Prospective evaluation of radiologically directed fine-needle aspiration biopsy of nonpalpable breast lesions. The application of fine-needle aspiration biopsy (FNAB) to the diagnosis of nonpalpable breast lesions was evaluated with a new method which uses standard needle localization under mammographic guidance to assure accurate sampling by FNAB. This method was prospectively applied to 100 mammographically detected breast lesions in 100 women (mean age, 53 years). All 100 patients underwent surgical excision of these nonpalpable lesions after cytologic aspiration. Sufficient aspirated material was obtained for cytologic diagnosis from 91 patients (91%). The histologic and cytologic interpretations were then compared. Twenty malignancies were ultimately diagnosed by histology (12 invasive ductal carcinoma, six ductal carcinoma in situ, and two lobular carcinoma in situ), of which 17 had been cytologically diagnosed. There were no false-positive diagnoses of malignancy by FNAB. False-negative readings (3.3%) included two cases of lobular carcinoma in situ and one case of ductal carcinoma in situ. This technique thus demonstrated a sensitivity of 85%, specificity of 100%, and overall diagnostic accuracy of 96.7% for the nonsurgical detection of malignancy in nonpalpable breast lesions. These results suggest that the established safety, reliability, and cost-effectiveness of FNAB can be maintained in this clinical setting. This procedure may obviate the need for open surgical biopsy in those patients with an unequivocal diagnosis of malignancy. It can also be done using standard techniques and equipment available in many community hospitals. 