The cytologic results of 44 consecutive fine-needle aspiration (FNA) biopsies of the pancreas are reported. The series consisted of 27 women and 17 men with an age range of 31-89 yr (mean, 61.5). Excluding insufficient cases, the sensitivity of the procedure was 88%, specificity was 100%, positive predicative value (PV) was 100%, negative PV was 69%, and efficiency of the test was 90%. There were 29 true-positive, four false-negative, and nine true-negative diagnoses. Two specimens were insufficient for diagnosis. Giant cells of varying types were seen in both the malignant and benign cases. Two of the benign cases demonstrated rare multinucleated foreign body-type giant cells, most likely representing the changes seen in pancreatitis. In 13 malignant cases, multinucleated tumor cells were present, while six additional cases had multinucleated benign histiocytes reflecting the associated pancreatitis. Two malignant cases each had tumor giant cells and benign multinucleated histiocytes. Three of the malignant cases had numerous multinucleated tumor giant cells arranged in a dissociative fashion with evidence of cytophagocytosis consistent with a pleomorphic giant-cell carcinoma of the pancreas. One additional case demonstrated numerous multinucleated osteoclastic-like cells consistent with an osteoclastic tumor of the pancreas. This article documents the accuracy of FNA biopsy of the pancreas and notes that giant cells of varying types can be found in pancreatic FNA biopsies. Appreciation of the various types of giant cells in pancreatic FNA biopsy is important for diagnostic accuracy and prognosis.