Methods, systems, and related computer program products for computer-aided detection (CAD) of anatomical abnormalities in digital (or digitized) x-ray mammograms are described. The inventive techniques are based on using a foundational CAD processing algorithm that is characterized by at least one of non-shift-invariance, non-rotational-invariance, and non-inversional-invariance. According to one preferred embodiment, a first x-ray mammogram image of a breast is received, and at least one altered version thereof is generated that differs therefrom by at least one of image shift, image rotation, and image inversion. The first x-ray mammogram image and each of the at least one altered versions thereof are individually processed using the foundational CAD algorithm to generate a respective plurality of individual CAD detection sets. The plurality of CAD detection sets are then compared to generate an overall CAD detection set.