Abstract: A system, method, and computer program product for registering two or more patient images for change assessment over time. An example aspect is configured to: obtain a new image of an area with an image capture system; obtain a reference image of a similar area; perform pre-processing of the new image and the reference image; perform a coarse alignment of the new image and the reference image; perform a high-resolution estimate; perform a high-resolution alignment; cross-check the at least one-point match to eliminate false matches and confirm correct matches of the high-resolution new image and the high-resolution reference image; perform segmentation of the high-resolution new image and the high-resolution reference image; perform analysis on at least one lesion in the high-resolution new image and the high-resolution reference image; and display a result of the analysis on a validator.