<PAGE>   1

   As filed with the Securities and Exchange Commission on December 15, 1999
   Registration Statement No. 333-
--------------------------------------------------------------------------------


                       SECURITIES AND EXCHANGE COMMISSION
                              Washington, DC 20549
                              --------------------


                                    FORM S-8
             REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933

                              ---------------------


                          VENTANA MEDICAL SYSTEMS, INC.
             (Exact Name of Registrant as Specified in Its Charter)


     Delaware                                           94-2976937
 (State or Other Jurisdiction of           (I.R.S. Employer Identification No.)
 Incorporation or Organization)


 3865 North Business Center Drive, Tucson, Arizona          85705
  (Address of Principal Executive Offices)               (Zip Code)

                       1998 Nonstatutory Stock Option Plan
                            (Full Title of the Plan)

                                   Jay Meridew
                            Vice President of Finance
                          Ventana Medical Systems, Inc.
                        3865 North Business Center Drive
                             Tucson, Arizona 85705
                     (Name and Address of Agent for Service)

                                 (520) 887-2155
          (Telephone Number, Including Area Code, of Agent for Service)

                                   Copies to:

                        Christian J. Hoffmann, III, Esq.
                               Streich Lang, P.A.
                                 Renaissance One
                            Two North Central Avenue
                             Phoenix, Arizona 85004
                                 (602) 229-5336

                         CALCULATION OF REGISTRATION FEE
<TABLE>
<CAPTION>
=======================================================================================================================
                                                            Proposed               Proposed
                                                            Maximum                Maximum            Amount of
 Title of Securities To Be             Amount To Be       Offering Price           Aggregate          Registration
       Registered                       Registered          Per Share(1)        Offering Price(1)         Fee
-----------------------------------------------------------------------------------------------------------------------
<S>                                      <C>                   <C>                 <C>                 <C>
Common Stock, $.001 par value            500,000                $23.75             $11,875,000          $3,135
per share
=======================================================================================================================
</TABLE>


(1)      Estimated pursuant to Rule 457(c) and (h) under the Securities Act of
         1933, as amended (the "Act"), solely for purposes of calculating the
         registration fee. The calculation is based on the average of the high
         and low prices as quoted on the Nasdaq National Market on December 9,
         1999 (the "Market Price").



<PAGE>   2

                                     PART II

               INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

ITEM 3.  INCORPORATION OF DOCUMENTS BY REFERENCE.

         The following documents and information previously filed with the
Securities and Exchange Commission (the "Commission") by Ventana Medical
Systems, Inc. (the "Company") are hereby incorporated by reference in this
Registration Statement:

         (1)      Annual Report on Form 10-K for the fiscal year ended December
                  31, 1998;

         (2)      Quarterly Report on Form 10-Q for the quarter ended March 31,
                  1999;

         (3)      Quarterly Report on Form 10-Q for the quarter ended June 30,
                  1999;

         (4)      Quarterly Report on Form 10-Q for the quarter ended September
                  30, 1999;

         (5)      Definitive Proxy Statement used in connection with the
                  Company's Annual Meeting of Stockholders held on May 6, 1999,
                  other than the portions of such document, which by statute, by
                  designation in such document or otherwise, are not deemed to
                  be filed with the Commission or are not required to be
                  incorporated herein by reference; and

         (6)      All documents subsequently filed by the Company pursuant to
                  Sections 13(a), 13(c), 14 and 15(d) of the Securities Exchange
                  Act of 1934, as amended (the "Exchange Act"), prior to the
                  filing of a post-effective amendment which indicates that all
                  securities registered have been sold or which deregisters all
                  securities then remaining unsold, shall be deemed to be
                  incorporated by reference in this Registration Statement and
                  to be part hereof from the date of filing of such documents.

ITEM 4.  DESCRIPTION OF SECURITIES.

         Not applicable.

ITEM 5.  INTERESTS OF NAMED EXPERTS AND COUNSEL.

         Not applicable.

ITEM 6.  INDEMNIFICATION OF DIRECTORS AND OFFICERS.

         Pursuant to Section 102(b)(7) of the Delaware General Corporation Law
(the "DGCL"), Article X of the Company's Restated Certificate of Incorporation
(the "Restated Certificate of Incorporation") eliminates the liability of the
Company's directors to the Company or its stockholders, except for liabilities
related to breach of duty of loyalty, actions not in good faith and certain
other liabilities.

         Section 145 of the DGCL provides for indemnification by the Company of
its directors and officers. In addition, Article VI of the Company's Bylaws
requires the Company to indemnify any current or former director or officer to
the fullest extent permitted by the DGCL. In addition, the Company has entered
into indemnity agreements with its directors and executive officers that
obligate the Company to indemnify such directors and executive officers to the
fullest extent permitted by the DGCL. The Company also maintains officers' and
directors' liability insurance, which insures against liabilities that officers
and directors of the Company may incur in such capacities.

ITEM 7.  EXEMPTION FROM REGISTRATION CLAIMED.

         Not applicable.

ITEM 8.  EXHIBITS.

         See the Exhibit Index at Page E-1 of this Registration Statement.

                                        2

<PAGE>   3

ITEM 9.  UNDERTAKINGS.

         A.       The undersigned Registrant hereby undertakes:

                  (1)      To file, during any period in which offers or sales
are being made, a post-effective amendment to this Registration Statement:

                           (i)   to include any prospectus required by Section
         10(a)(3) of the Securities Act of 1933;

                           (ii)  to reflect in the prospectus any facts or
         events arising after the effective date of the Registration Statement
         (or the most recent post-effective amendment thereof), which,
         individually or in the aggregate, represent a fundamental change in the
         information set forth in the Registration Statement; and

                           (iii) to include any material information with
         respect to the plan of distribution not previously disclosed in the
         Registration Statement or any material change to such information in
         the Registration Statement.

         Provided, however, that paragraph (A)(1)(i) and (A)(1)(ii) do not apply
         if the Registration Statement is on Form S-3 or Form S-8, and the
         information required to be included in a post-effective amendment by
         those paragraphs is contained in periodic reports filed by the
         Registrant pursuant to Section 13 or Section 15(d) of the Securities
         Exchange Act of 1934 that are incorporated by reference in the
         Registration Statement.

                (2)      That, for the purpose of determining any liability
under the Securities Act of 1933, each such post-effective amendment shall be
deemed to be a new registration statement relating to the securities offered
therein, and the offering of such securities at that time shall be deemed to be
the initial bona fide offering thereof.

                (3)      To remove from registration by means of a
post-effective amendment any of the securities being registered which remain
unsold at the termination of the offering.

         B.     The undersigned Registrant undertakes that, for purposes of
determining any liability under the Securities Act of 1933, each filing of the
registrant's annual report pursuant to Section 13(a) or Section 15(d) of the
Securities Exchange Act of 1934 that is incorporated by reference in this
Registration Statement shall be deemed to be a new registration statement
relating to the securities offered therein, and the offering of such securities
at that time shall be deemed to be the initial bona fide offering thereof.

         C.     Insofar as indemnification for liabilities arising under the
Securities Act of 1933 may be permitted to Directors, officers and controlling
persons of the Company pursuant to the foregoing provisions described under Item
6 above, or otherwise, the Company has been advised that in the opinion of the
Securities and Exchange Commission such indemnification is against public policy
as expressed in the Securities Act of 1933 and is, therefore, unenforceable. In
the event that a claim for indemnification against such liabilities (other than
the payment by the Company of expenses incurred or paid by a Director, officer
or controlling person of the Company in the successful defense of any action,
suit or proceeding) is asserted by such Director, officer or controlling person
in connection with the securities being registered, the Company will, unless in
the opinion of its counsel the matter has been settled by controlling precedent,
submit to a court of appropriate jurisdiction the question whether such
indemnification by it is against public policy as expressed in the Securities
Act of 1933 and will be governed by the final adjudication of such issue.



                                        3


<PAGE>   4

                                   SIGNATURES

         Pursuant to the requirements of the Securities Act, the Registrant
certifies that it has reasonable grounds to believe that it meets all of the
requirements for filing on Form S-8 and has duly caused this Registration
Statement to be signed on its behalf by the undersigned, hereunto duly
authorized, in the City of Tucson, State of Arizona, on this 15th day of
December, 1999.


                                              VENTANA MEDICAL SYSTEMS, INC.



                                              By: /s/ Jay Meridew
                                                 Jay Meridew, Vice President and
                                                 Chief Financial Officer


                                POWER OF ATTORNEY

         KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature
appears below hereby constitutes and appoints Jay Meridew and Christopher M.
Gleeson and each of them acting individually, as his attorney-in-fact, each with
full power of substitution, for him in any and all capacities, to sign any and
all amendments to this Registration Statement on Form S-8, and to file the same,
with exhibits thereto and other documents in connection therewith, with the
Securities and Exchange Commission, hereby ratifying and confirming all that
said attorney-in-fact, or his substitutes, may do or cause to be done by virtue
hereof.

         Pursuant to the requirements of the Securities Act of 1933, this
Registration Statement has been signed by the following persons in the
capacities indicated:


<TABLE>
<CAPTION>

     SIGNATURE                         TITLE                                                    DATE
<S>                               <C>                                                      <C>
 /s/ Christopher M. Gleeson       President and Chief Executive Officer                    December 15, 1999
---------------------------
Christopher M. Gleeson            (Principal Executive Officer)


 /s/ Jay Meridew                  Vice President, Chief Financial Officer and Secretary    December 15, 1999
---------------------------
Jay Meridew                       (Principal Financial and Accounting Officer)


 /s/ Edward M. Giles              Director                                                 December 15, 1999
--------------------------
Edward M. Giles


 /s/ Thomas M. Grogan             Director                                                 December 15, 1999
--------------------------
Thomas M. Grogan


 /s/ John Patience                Director                                                 December 15, 1999
--------------------------
John Patience


 /s/ Jack W. Schuler              Director                                                 December 15, 1999
--------------------------
Jack W. Schuler


 /s/ James R. Weersing            Director                                                 December 15, 1999
--------------------------
James R. Weersing


 /s/ Rex J. Bates                 Director                                                 December 15, 1999
--------------------------
Rex J. Bates


 /s/ Henry T. Pietraszek          Director                                                 December 15, 1999
--------------------------
Henry T. Pietraszek
</TABLE>



                                                         4
<PAGE>   5

                          VENTANA MEDICAL SYSTEMS, INC.

                       REGISTRATION STATEMENT ON FORM S-8

                                INDEX TO EXHIBITS


Exhibit
Number            Description
-------           -----------

4.1               1998 Nonstatutory Stock Option Plan with forms of agreements
                  used thereunder

5.1               Opinion of counsel as to legality of securities being
                  registered

23.1              Consent of counsel (contained in Exhibit 5.1 hereto)

23.2              Consent of Ernst & Young LLP

24.1              Powers of Attorney (contained in signature pages on page 4 of
                  this registration statement)


                                                      E-1