Simultaneous grayscale and geometric registration of images, such as mammograms, facilitates temporal comparison and enhances the speed and reliability of computer aided diagnosis (CAD) detection of medical abnormalities. The method generally includes optimizing a merit function, e.g., sum of squared errors, containing parameters associated with a transformation function for simultaneous geometric and grayscale registering of the images, the optimizing of the merit function being performed by determining optimal values of the parameters using data in the images and registering one image to the other by applying the geometric and grayscale transformation function using the optimal values of the parameters. The optimizing may be performed iteratively from coarse to fine resolutions using a modified Levenberg-Marquardt method for optimizing nonlinear parameters with linear regression for optimizing linear parameters. A final iteration may be performed after removing pixel value pairs from the images that correspond to outliers of a joint pixel value histogram.