Method for optical scanning of at least one object region placed on a transparent specimen holder comprising a histological tissue sample, the method comprising: for each sample lateral position of plural predefined sample lateral positions (x0,x1,x2) performing a focus determination by: performing laser reflection and using a first camera taking plural first images to determine a reference distance (rd) between the specimen holder and an objective lens; performing transmission flash illumination and using a second camera taking plural second images to define a focus distance taking into account the reference distance (rd); after completing the focus determination, determining a focus distance topology (600, 700) across the object region based on the focus distances determined for all sample lateral positions (x0,x1,x2); and laterally moving the specimen holder and acquiring third images while focusing according to the focus distance topology (600, 700), wherein determining the reference distance comprises: translating the specimen holder such that the sample lateral position is located in an optical axis of the objective lens above the object region; traversing the objective lens by said laser beam to illuminate the object region at the sample lateral position; varying a distance between the specimen holder and the objective lens, meanwhile receiving light returning from the object region, comprising reflection form a dichroic filter/reflector, upon laser beam illumination, at the first camera, to acquire plural first images; analyzing the first images to detect the reference distance (rd) at which the laser beam is substantially focused at and reflected from an upper surface of the specimen holder, wherein analyzing the first images further comprises detecting a first reflex of the laser beam at an upper surface of a cover glass covering the object region; detecting a second reflex of the laser beam at a lower surface of the cover glass; detecting a third reflex of the laser beam at the upper surface of the specimen holder. performing laser reflection and using a first camera taking plural first images to determine a reference distance (rd) between the specimen holder and an objective lens; performing transmission flash illumination and using a second camera taking plural second images to define a focus distance taking into account the reference distance (rd); after completing the focus determination, determining a focus distance topology (600, 700) across the object region based on the focus distances determined for all sample lateral positions (x0,x1,x2); and laterally moving the specimen holder and acquiring third images while focusing according to the focus distance topology (600, 700), wherein determining the reference distance comprises: translating the specimen holder such that the sample lateral position is located in an optical axis of the objective lens above the object region; traversing the objective lens by said laser beam to illuminate the object region at the sample lateral position; varying a distance between the specimen holder and the objective lens, meanwhile receiving light returning from the object region, comprising reflection form a dichroic filter/reflector, upon laser beam illumination, at the first camera, to acquire plural first images; analyzing the first images to detect the reference distance (rd) at which the laser beam is substantially focused at and reflected from an upper surface of the specimen holder, wherein analyzing the first images further comprises detecting a first reflex of the laser beam at an upper surface of a cover glass covering the object region; detecting a second reflex of the laser beam at a lower surface of the cover glass; detecting a third reflex of the laser beam at the upper surface of the specimen holder. translating the specimen holder such that the sample lateral position is located in an optical axis of the objective lens above the object region; traversing the objective lens by said laser beam to illuminate the object region at the sample lateral position; varying a distance between the specimen holder and the objective lens, meanwhile receiving light returning from the object region, comprising reflection form a dichroic filter/reflector, upon laser beam illumination, at the first camera, to acquire plural first images; analyzing the first images to detect the reference distance (rd) at which the laser beam is substantially focused at and reflected from an upper surface of the specimen holder, wherein analyzing the first images further comprises detecting a first reflex of the laser beam at an upper surface of a cover glass covering the object region; detecting a second reflex of the laser beam at a lower surface of the cover glass; detecting a third reflex of the laser beam at the upper surface of the specimen holder.