CR (Computed Radiography) is characterized by high sensitivity and wide dynamic range. Moreover, it has the advantage of being able to transfer exposed images directly to a computer-aided detection (CAD) system which is not possible using conventional film digitizer systems. This paper proposes a high-performance clustered microcalcification detection system for CR mammography. Before detecting and classifying candidate regions, the system preprocesses images with a normalization step to take into account various imaging conditions and to enhance microcalcifications with weak contrast. Large-scale experiments using images taken under various imaging conditions at seven hospitals were performed. According to analysis of the experimental results, the proposed system displays high performance. In particular, at a true positive detection rate of 97.1%, the false positive clusters average is only 0.4 per image. The introduction of geometrical features of each microcalcification for identifying true microcalcifications contributed to the performance improvement. One of the aims of this study was to develop a system for practical use. The results indicate that the proposed system is promising.