Large core needle biopsy is a common procedure used to obtain histological samples when cancer is suspected in diagnostic breast images. The procedure is typically performed under image guidance, with freehand ultrasound and stereotactic mammography (SM) being the most common modalities used. To utilize the advantages of both modalities, a biopsy device combining three-dimensional ultrasound (3DUS) and digital SM imaging with computer-aided needle guidance was developed. An implementation of a stereo camera method was applied to SM calibration, providing a target localization error of 0.35 mm. The 3-D transformation between the two imaging modalities was then derived, with a target registration error of 0.52 mm. Finally, the needle guidance error of the device was evaluated using tissue-mimicking phantoms, showing a sample mean and standard deviation of 0.44 +/- 0.22 and 0.49 +/- 0.27 mm for targets planned from 3DUS and SM images, respectively. These results suggest that a biopsy procedure guided using this device would successfully sample breast lesions at a size greater than or equal to the smallest typically detected in mammographic screening (approximately 2 mm).