Summary The coupling of advanced computer-assisted software technology to hardware and manufacturing initiatives has ushered in an era in which percutaneous core biopsy of nonpalpable breast lesions detected by screening mammography is feasible and virtually equivalent in accuracy to radiographically localized excisional biopsy for appropriately chosen cases. Indeed, most (though not all) lesions are candidates for this procedure. Although it has not been discussed herein, ultrasound guided CNB may be another option. CNB under guidance of magnetic resonance imaging is also under investigation. To be successful, a CNB program must follow basic patterns of preferred medical practice: proper lesion selection, adequate and calibrated technology, experience in image interpretation and guidance of biopsy, and reconciliation of image and histological findings. The actual biopsy procedure may be the simplest component of the equation.