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                                                                   EXHIBIT 10.42


September 29, 2000


Mr. Paul R. Hamelin
47 Mark Drive
Hawthorne Woods, IL  60047

Dear Paul,

This letter supersedes and replaces our original offer letter sent to you, dated
August 9, 2000.

On behalf of Millennium Pharmaceuticals, Inc. (the "Company"), I am pleased to
offer you the position of Senior Vice President, Commercial Operations reporting
to Mark Levin, CEO.

1.   EFFECTIVE DATE: The effective date of your full-time employment with the
     Company is to be determined upon your formal acceptance of this offer.
     After discussion with the hiring manager, please contact Shana Stevens at
     617-551-7889 to confirm your start date.

2.   SALARY: Your base salary will initially be $300,000 per annum. Your salary
     will be paid periodically in accordance with the Company's payroll
     procedures. In addition, in accordance with the Company's compensation
     practices, you will receive, approximately annually, a salary review which
     will be based on your performance, the Company's performance and such other
     factors as may be determined by the Company's Board of Directors.

3.   SUCCESS SHARING: You will be eligible to participate in the 2000 Millennium
     Success Sharing cash bonus program, which includes a fixed percentage of
     salary target for each position. The funding of the target is based on the
     Company meeting overall goals for 2000. In the event of Company performance
     below or above target, your personal bonus target may vary. Your individual
     bonus payment will also vary based on your individual performance. The
     target for your position is 12% of your annual salary, prorated for your
     length of active service in the calendar year of 2000. Your manager will
     work with you to establish your individual goals, which will be the primary
     factor in determining your bonus payment. Bonus payments will be made to
     eligible and active employees in March of 2001 for the 2000 Success Sharing
     Plan.

4.   BENEFITS: You and your dependents will be eligible for the Company's
     standard medical, dental, life insurance, disability benefits and Section
     125 cafeteria plan. After the standard waiting periods, you will also be
     eligible to participate in the Company's 401(k) and Employee Stock Purchase
     plans. You will accrue vacation at the rate of 1.25 days per month of
     full-time employment. Standard paid holidays will be observed.
     Transportation benefits, including a choice of MBTA pass up to $60 or
     contributory off-site parking, are also available. The Company, however,
     reserves the right to modify its employee benefit programs from
     time-to-time.

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Mr. Paul R. Hamelin
September 29, 2000
Page 2

5.   EQUITY PARTICIPATION, VESTING OF STOCK: Subject to approval by the
     Company's Board of Directors, you will be granted a stock option
     exercisable for 125,000 shares of the Company's Common Stock at an exercise
     price equal to the current fair market value of the Company's Common Stock
     as determined by the Company's Board of Directors. This option will vest as
     to one fourth (1/4) of the shares on the first anniversary of your
     commencement of full-time employment with the Company and as to one
     forty-eighth (1/48) of the shares at the end of each full month thereafter
     until all shares are vested, provided that you remain employed by the
     Company. In the event of your death or total and permanent disability (as
     defined in the Internal Revenue Code of 1986, as amended) during the first
     year of your employment, the initial one-fourth (1/4) of your shares that
     would have vested at the end of your first year of employment shall vest.
     In the event of termination of your employment for any reason (except as
     set forth in the preceding sentence), vesting shall cease. Please refer to
     the Company's Incentive Stock Plan for complete details. The number of
     shares subject to this option, and the exercise price (if the exercise
     price is set by the Millennium Board of Directors prior to the effective
     date of the split) will be adjusted to reflect the two-for-one stock split
     approved by the Company's Board of Directors to become effective October
     18, 2000.

6.   EMPLOYMENT PERIOD: Your employment with the Company will be at-will,
     meaning that you will not be obligated to remain employed by the Company
     for any specified period of time; likewise, the Company will not be
     obligated to continue your employment for any specific period and may
     terminate your employment at any time, with or without cause.

7.   EMPLOYMENT ELIGIBILITY VERIFICATION: Please note that all persons employed
     in the United States, are required to complete an Employment Eligibility
     Verification Form on the first day of employment and submit an original
     document or documents that establish identity and employment eligibility
     within three business days of employment. For your convenience, we are
     enclosing Form I-9 for your review. You will need to complete Section 1 and
     present original document(s) of your choice as listed on the reverse side
     of the form once you begin work. PLEASE NOTE: THE I-9 FORM AND VALID
     IDENTIFICATION ARE LEGAL REQUIREMENTS AND MUST BE SUBMITTED WITHIN 3 DAYS
     OF YOUR START DATE. IF YOU DO NOT SUBMIT THE REQUIRED DOCUMENTATION WITHIN
     THE 3-DAY TIME FRAME, BY LAW WE CANNOT ALLOW YOU TO CONTINUE TO WORK.

8.   PROPRIETARY INFORMATION, NO CONFLICTS: You agree to execute the Company's
     standard form of Invention, Non-Disclosure and Non-Competition Agreement
     and to be bound by all of the provisions thereof. You hereby represent that
     you are not presently bound by any employment agreement, confidential or
     proprietary information agreement or similar agreement with any current or
     previous employer that would impose any restriction on your acceptance of
     this offer or that would interfere with your ability to fulfill the
     responsibilities of your position with the Company.

9.   MEDICAL SURVEILLANCE: As part of Millennium's medical surveillance program,
     employees are required to have an initial physical, provided by an on-site
     registered nurse. All laboratory employees working with hazardous chemical,
     infectious agents, radio labeled materials or animals shall have access to
     medical attention, including initial and periodic medical exams without
     cost to

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Mr. Paul R. Hamelin
September 29, 2000
Page 3

     the employee or loss of pay. An employee may refuse an exam if he/she signs
     a release. If you want to decline from having the initial physical, please
     notify Human Resources on your first day at New Employee Orientation. Your
     initial surveillance examination will be scheduled to take place during the
     first week of your employment.

10.  NEW EMPLOYEE ORIENTATION: On the first Monday of your employment with the
     Company, you should arrive at our 75 Sidney Street at location for New
     Employee Orientation. Millennium is located at University Park at 75 Sidney
     Street, and orientation is held on the 1st floor. If taking the MBTA you
     will get off at the Central Square stop on the Red Line. Directions for
     driving are enclosed. Millennium will reimburse you for any parking
     expenses. Orientation will begin promptly at 8:30 a.m.

11.  SIGN-ON BONUS: The Company will pay you a bonus of $75,000 per year for two
     years. The first payment will be made on the date of the first paycheck
     following commencement of your full time employment. Should you terminate
     for any reason within 12 months of your starting date after having received
     you bonus, the Company reserves the right to seek repayment of all or a
     pro-rata portion of your bonus. The second $75,000 will be paid with the
     paycheck following the one year anniversary of the commencement of your
     full-time employment. The Company reserves the right to seek repayment of a
     pro-rata portion of this bonus should you terminate for any reason during
     the following 12 months.

12.  FORGIVABLE LOAN: The Company will loan you a total of $250,000, payable to
     you on the date of your first paycheck following commencement of your full
     time employment. This loan (with interest), which will be forgivable over a
     four-year period, will be granted pursuant to the terms and conditions of a
     loan agreement which will be forwarded to you under separate cover.
     One-fourth of the principal and interest will be forgiven on the one year
     anniversary of your full-time employment with the Company, and one
     forty-eighth (1/48) of the loan will be forgiven at the end of each full
     month thereafter until the entire loan has been forgiven, provided that you
     remain employed by the Company. In the event of your termination from the
     Company, the principal balance and interest will be due. The loan will be
     secured by a second mortgage on your principal residence.

13.  RELOCATION EXPENSES: Upon your acceptance of this offer, you are eligible
     for reimbursement of the following expenses associated with your
     relocation. SPECIFIC RELOCATION INFORMATION WILL FOLLOW FROM MSI,
     MILLENNIUM'S RELOCATION COMPANY.

     -    Reimbursement for expenses associated with direct-route transportation
          to Cambridge.
     -    The cost of packing, moving, 60 days' temporary storage, and unloading
          of your household goods and effects using a certified carrier of the
          Company's choice.
     -    Temporary housing for two months upon your arrival in the Boston area
          or $3,000 (grossed up) lump sum if housing is not used.
     -    Destination services provided by Corporate Real Estate Services, a
          division of Hunneman Coldwell Banker.

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Mr. Paul R. Hamelin
September 29, 2000
Page 4

     -    Closing costs (excluding points) on the purchase of a new home, up to
          3% of the purchase price, if purchased within 12 months of your date
          of hire.
     -    Closing costs, up to 6% of the sale price, on the sale of your primary
          residence if sold within 12 months of your date of hire.
     -    The Company will provide a lump sum allowance of $2,000 (grossed up)
          to cover additional relocation related expenses. This sum will be paid
          to you by MSI once you submit a request for payment. Should you
          voluntarily resign from the Company within one year of relocating, the
          Company reserves the right to seek repayment of the entire amount.
     -    Up to two house-hunting trips, for up to eight (8) days, for the
          purpose of locating suitable housing.

Should you voluntarily resign from the Company within one year of relocating,
the Company reserves the right to seek repayment of ALL REIMBURSED RELOCATION
EXPENSES.

Paul, all of us here at Millennium are very enthusiastic about your commitment
to joining the Company and have the highest expectation of your future
contributions.

Please indicate your acceptance of the foregoing by signing the enclosed copy of
this letter and returning it to Shani Stickney no later than October 6, 2000.
After that date, the offer will lapse.

Very truly yours,
MILLENNIUM PHARMACEUTICALS, INC.

/s/ LINDA K. PINE

Linda K. Pine
Sr. Vice President
Human Resources

The foregoing is signed and accepted as of the date first above written by:


/s/ PAUL R. HAMELIN
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Paul R. Hamelin                                     Date