Nonpalpable breast lesions in 20 female patients were prospectively evaluated with a new technique of fine-needle aspiration biopsy (FNAB) under mammographic guidance. The patient age range was 37-82 years (mean: 60 years), and the mammographic indications for biopsy were microcalcifications (30%), mass (30%), mass with calcifications (25%), and asymmetric density (15%). Seven (35%) patients had significant risk factors for breast cancer. Prototype coaxial 19-gauge/22-gauge and 18-gauge/20-gauge needle systems (Cook, Inc., Bloomington, IN) were used for localization and biopsy. The technique involved needle localization of the target lesion with FNAB performed through the localizing needle after radiologic confirmation of position. A localizing wire then was inserted to allow each patient to proceed directly to the operating room for a standard needle localization open biopsy. Successful localization and aspiration was possible in 18 (90%) patients. Surgical excision was performed in all 20 patients and confirmed by specimen radiography in 17 (85%). A significant concordance of 94 per cent was found between the histologic results of the open biopsy specimens and the cytologic findings of aspirated specimens. These findings suggest that mammographically guided FNAB may offer a safe, reliable, and cost-effective alternative to open biopsy of nonpalpable breast lesions. Further study of this procedure is warranted to confirm its potential in this area.