OBJECTIVE Imaging-directed fine-needle aspiration biopsy can be performed with or without immediate cytologic assessment (smears). We compared the results obtained immediately from cytologic smears with the results of cell-block analysis. We wished to determine the frequency of false-negative findings on cytologic smears in patients subsequently found to have malignant tumors by cell-block analysis. METHODS We retrospectively reviewed the records for 100 consecutive biopsies performed between January 1986 and August 1987. In each case, specimens were obtained from both a 22-gauge and a 20-gauge notched needle placed in tandem. The study group consisted of 84 patients who had results of analyses of both cytologic smears and cell blocks available for review and who had clinical or surgical correlation. RESULTS Sixty-four (76%) of the 84 biopsies yielded malignant tumor cells, 11 yielded evidence of a benign process, and nine were not diagnostic. Malignant tumor cells were seen on the cytologic smears in 55 (86%) of the 64 patients who had malignant tumors; in the other nine patients, the malignant tumors were indicated by the cell-block analysis only. Within the group of benign disorders, in only one case (9%) was the cell block diagnostic when the cytologic smear was not. CONCLUSIONS Operators performing fine-needle aspiration biopsy should be aware of the limitations of immediate cytologic evaluation. Cell-block analysis of the aspirate remaining after the smears are made can be expected to increase the diagnostic accuracy in up to 14% of patients.