AbstractFine‐needle aspiration (FNA) has played a significant role in the diagnosis of pancreatic masses but false‐positive diagnoses occur.The Anatomic Pathology files were searched for FNAs of pancreas with subsequent resections. FNAs with a diagnosis of positive for or suspicious for adenocarcinoma followed by a benign resection specimen were reviewed and the surgical pathology and cytology findings correlated.Six cases had a cytologic diagnosis of adenocarcinoma or suspicious for adenocarcinoma but resection specimens were benign. In two cases, a non‐invasive intraductal papillary mucinous neoplasm (IPMN) without significant dysplasia was present surrounded by foci of pancreatic intraepithelial neoplasia (PanIN). In both cases, the degree of atypia within the IPMN was less than that seen cytologically. The nuclear features of the PanIN overlapped those seen in the smears. In two cases, a neuroendocrine neoplasm was present accompanied by multifocal PanIN. The cytologic features of the neuroendocrine neoplasm did not correlate with the material cytologically diagnosed as adenocarcinoma. The cytologically atypical epithelium was similar to the PanIN. Two diagnoses of adenocarcinoma were made cytologically but the pancreatectomy specimens revealed pancreatitis with reactive atypia.Cytologic diagnosis of pancreatic adenocarcinoma has high specificity. Six cytologic misdiagnoses of adenocarcinoma occurred in 105 patients. The cytologic features of these misdiagnoses correlated with histopathologic changes of intermediate to high‐grade PanIN or marked reactive atypia in severe pancreatitis. PanIN may be an under recognized, but significant source of false‐positive results. Diagn. Cytopathol. 2011. © 2010 Wiley‐Liss, Inc.