Methods and systems for automatically generating a mask delineating a region of interest (ROI) within an image containing skin are disclosed. The image may be of an anatomical area containing skin, such as the face, neck, chest, shoulders, arms or hands, among others, or may be of portions of such areas, such as the cheek, forehead, or nose, among others. The mask that is generated is based on the locations of anatomical features or landmarks in the image, such as the eyes, nose, eyebrows and lips, which can vary from subject to subject and image to image. As such, masks can be adapted to individual subjects and to different images of the same subjects, while delineating anatomically standardized ROIs, thereby facilitating standardized, reproducible skin analysis over multiple subjects and/or over multiple images of each subject. Moreover, the masks can be limited to skin regions that include uniformly illuminated portions of skin while excluding skin regions in shadow or hot-spot areas that would otherwise provide erroneous feature analysis results. Methods and systems are also disclosed for automatically registering a skin mask delineating a skin ROI in a first image captured in one imaging modality (e.g., standard white light, UV light, polarized light, multi-spectral absorption or fluorescence imaging, etc.) onto a second image of the ROI captured in the same or another imaging modality. Such registration can be done using linear as well as non-linear spatial transformation techniques.