A computer simulation of stereotactic breast biopsy was developed that paralleled the geometric configuration of a currently available breast biopsy system. This model was developed to define and improve the targeting of breast lesions with stereotactic biopsy techniques. Lesions must be clearly identified and accurately targeted on both views for successful localization. Nonvisualization of a lesion may result from overlying tissue or from the geometric configuration of the imaging system. Familiarity with the geometric configuration of the biopsy unit, especially the location of the reference point and center of rotation, facilitates understanding of apparent changes in lesion position (parallax shift). Inaccuracy in lesion targeting on one or both views will manifest predominantly as an error in the calculated z value (depth). The magnitude and direction of this error are largely determined by the direction of the targeting error. Compensatory strategies include use of a long-throw core biopsy gun or directional vacuum-assisted biopsy device and additional sampling along the z axis and should be accompanied by critical evaluation of both pre- and postfire images. Understanding geometric considerations as well as how targeting accuracy affects accuracy in lesion localization should lead to greater success in sampling even challenging breast lesions at stereotactic biopsy.