Systems and methods for assessing virtual microscope slide image quality are provided. In order to determine whether a virtual slide image has any out of focus areas and is therefore a candidate for manual inspection, the various focus points used to scan the virtual slide image are used to calculate a best fit surface for the virtual slide image. The distance of each focus point from the best fit surface is then calculated and the largest distance is compared to a predetermined value. If the largest distance from a focus point to the best fit surface is larger than the predetermined value, then the virtual slide image is designated as needing a manual inspection and possible re-scan.