An instrument and method for scanning large microscope specimen on a specimen holder has a scanning optical microscope that is configured to scan the specimen in one of brightfield and fluorescence. The specimen is dynamically tillable about a scan direction during a scan to maintain focus along the length of each scan line as the scan proceeds. A three dimensional image of the specimen can be obtained wherein the specimen tilt and relative focus are maintained from a first image contour to a second image contour through a thickness of a specimen.