We evaluated the immunocytochemical (ICC) expression of K homology domain containing protein overexpressed in cancer (KOC) in pancreatic endoscopic ultrasound-guided fine needle aspirates (EUS-FNAs) to assess its potential use as an adjunct in differentiating nonneoplastic (GI epithelium) and benign neoplastic epithelia (benign epithelial pancreatic neoplasms) from pancreatic adenocarcinoma cells. Forty-eight cases of EUS-FNAs with histological and/or clinical follow-up data were selected for this study. Alcohol-fixed and PAP-stained slides were stained with monoclonal antibody to KOC/L523S (clone 69.1). Results were recorded as negative or positive. KOC expression was present in 35/40 (88%) of adenocarcinomas (Ac) and was negative in all eight benign cases. The sensitivity and specificity were as follows: cytology 85 and 100%, KOC 88 and 100%; combination of cytology and KOC 95 and 100%. We conclude that KOC ICC expression on alcohol-fixed smears along with cytology improves the sensitivity of EUS-FNAs in the diagnosis of pancreatic Ac, and KOC reactivity is especially useful in differentiating Ac from nonneoplastic gastrointestinal epithelium and benign neoplastic epithelia.