This paper describes a pattern recognition architecture, which we term hierarchical pyramid/neural network (HPNN), that learns to exploit image structure at multiple resolutions for detecting clinically significant features in digital/digitized mammograms. The HPNN architecture consists of a hierarchy of neural networks, each network receiving feature inputs at a given scale as well as features constructed by networks lower in the hierarchy. Networks are trained using a novel error function for the supervised learning of image search/detection tasks when the position of the objects to be found is uncertain or ill defined. We have evaluated the HPNN’s ability to eliminate false positive (FP) regions of interest generated by the University of Chicago’s (UofC) Computer-aided diagnosis (CAD) systems for microcalcification and mass detection. Results show that the HPNN architecture, trained using the uncertain object position (UOP) error function, reduces the FP rate of a mammographic CAD system by approximately 50% without significant loss in sensitivity. Investigation into the types of FPs that the HPNN eliminates suggests that the pattern recognizer is automatically learning and exploiting contextual information. Clinical utility is demonstrated through the evaluation of an integrated system in a clinical reader study. We conclude that the HPNN architecture learns contextual relationships between features at multiple scales and integrates these features for detecting microcalcifications and breast masses.