Intraoperative evaluation of nonpalpable breast lesions by frozen section frequently is not performed because of potential tissue loss, sampling errors and frozen section artifacts. In a retrospective review we found that only 50 of 503 needle-localized breast biopsies (NLBBs) were evaluated at our institution by frozen section (FS), with a sensitivity of 88%. However, intraoperative evaluation of such lesions may be essential to single-stage and cost-effective management. To this end, this study evaluated the diagnostic accuracy and potential clinical role of intraoperative imprint cytology (IIC) in NLBB. A total of 88 lesions were evaluated by IIC and permanent histology. Fifteen of them were also concomitantly evaluated by FS. All but one deferred cytologic diagnoses were correct. Twelve of 15 FS diagnoses were correct, 2 were deferred, and 1 was false negative. The data suggest that IIC may circumvent some of the difficulties associated with FS, thereby allowing immediate clinical management and later definitive histologic typing and evaluation of prognostic parameters in nonpalpable breast lesions.