The present invention relates to a system (1) and method for registration of medical image (10,11). Furthermore the invention relates to a computer program (5) for registration of medical images (10,11), when the computer program (5) is executed in a computer (2). In order to provide a more accurate registration transformation of medical images it is suggested to detect insufficiently similar areas (14,14’,25,26) and to exclude them from the registration by means of an exclusion mask (22,24,27) that indicates which pixels/voxels should not be included during the registration process.