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Clusters of microcalcifications in mammograms are an important early sign of breast cancer. This paper presents a computer-aided diagnosis (CAD) system for the automatic detection of clustered microcalcifications in digitized mammograms. The proposed system consists of two main steps. First, potential microcalcification pixels in the mammograms are segmented out by using mixed features consisting of wavelet features and gray level statistical features, and labeled into potential individual microcalcification objects by their spatial connectivity. Second, individual microcalcifications are detected by using a set of 31 features extracted from the potential individual microcalcification objects. The discriminatory power of these features is analyzed using general regression neural networks via sequential forward and sequential backward selection methods. The classifiers used in these two steps are both multilayer feedforward neural networks. The method is applied to a database of 40 mammograms (Nijmegen database) containing 105 clusters of microcalcifications. A free-response operating characteristics (FROC) curve is used to evaluate the performance. Results show that the proposed system gives quite satisfactory detection performance. In particular, a 90% mean true positive detection rate is achieved at the cost of 0.5 false positive per image when mixed features are used in the first step and 15 features selected by the sequential backward selection method are used in the second step. However, one must be cautious when interpreting the results, since the 20 training samples are also used in the testing step.