Artificial neural networks have been applied to the differentiation of actual “true” clusters from normal parenchymal patterns and also to the differentiation of actual clusters from false‐positive clusters as reported by a computerized scheme for the detection of microcalcifications in digital mammograms. The differentiation was carried out in both the spatial and frequency domains. The performance of the neural networks was evaluated quantitatively by means of receiver operating characteristic (ROC) analysis. It was found that the networks could distinguish clustered microcalcifications from normal nonclustered areas in the frequency domain, and that they could eliminate approximately 50% of false‐positive clusters of microcalcifications while preserving 95% of the positive clusters, when applied to the results of the automated detection scheme. A large, comprehensive training database is needed for neural networks to perform reliably in clinical situations.