A method and system for creating a digital, virtual slide having optimum image quality characteristics. Multiple regions of a physical slide are identified as well as at least two focus z-positions z1, and z2. Each region of the physical slide is scanned (imaged) at the first z position, so as to produce a first set of digital images of each defined region. Each region of the physical slide is also scanned (imaged) at the second z position, so as to produce a second set of digital images of each defined region. Each image of each set is evaluated against a focus quality metric and, for each region, either the first or second image, corresponding to that region, is selected that exhibits a focus quality metric corresponding to a desired focus quality. These images are then merged into a digital virtual slide. Additional focus z-positions may be included, and the multiple z-positions may be scanned seriatim, sequentially, and/or in overlapping fashion.