Computer-aided diagnosis techniques in medical imaging are developed for the automated differentiation between benign and malignant lesions and go beyond computer-aided detection by providing cancer likelihood for a detected lesion given image and/or patient characteristics. The goal of this study was the development and evaluation of a computer-aided detection and diagnosis algorithm for mammographic calcification clusters. The emphasis was on the diagnostic component, although the algorithm included automated detection, segmentation, and classification steps based on wavelet filters and artificial neural networks. Classification features were selected primarily from descriptors of the morphology of the individual calcifications and the distribution of the cluster. Thirteen such descriptors were selected and, combined with patient's age, were given as inputs to the network. The features were ranked and evaluated for the classification of 100 high-resolution, digitized mammograms containing biopsy-proven, benign and malignant calcification clusters. The classification performance of the algorithm reached a 100% sensitivity for a specificity of 85% (receiver operating characteristic area index Az = 0.98 +/- 0.01). Tests of the algorithm under various conditions showed that the selected features were robust morphological and distributional descriptors, relatively insensitive to segmentation and detection errors such as false positive signals. The algorithm could exceed the performance of a similar visual analysis system that was used as basis for development and, combined with a simple image standardization process, could be applied to images from different imaging systems and film digitizers with similar sensitivity and specificity rates.