Abstract: The purpose of the study was to demonstrate the feasibility of a hybrid functional/anatomic breast imaging platform with biopsy capability for facilitating lesion detection and diagnosis. This platform consists of an investigative dedicated positron emission mammography (PEM) device mounted on a stereotactic X-ray mammography system, permitting sequential acquisition of mammographic and emission images during a single breast compression. There is automatic coregistration of images from both modalities, and these results can be successfully correlated with histopathologic findings. The potential utility of functional images correlated to anatomic images would include noninvasively detecting clinically and radiographically occult cancers, assessing response to therapy, discriminating between benign and malignant breast masses, and ultimately reducing the number of invasive and costly surgical interventions. A spot-digital mammogram and subsequent PEM image, collected over a 4-minute period, were obtained in a single patient with the breast in compression after intravenous injection of (F-18)-2-deoxy-2-fluoro-D-glucose (FDG) at the time of stereotactic biopsy. The authors conclude that FDG-based lesion localization information may be combined with the lesion X-ray attenuation characteristics using this common imaging platform.