BACKGROUND. Mucins are high molecular weight glycoproteins that are produced by various epithelial cells including those found in the pancreas. MUC1 and MUC2 are two well characterized mucin antigens. The objective of the current study was to examine the pattern of phenotypic expression of MUC1 and MUC2 in pancreatic lesions obtained by fine-needle aspiration biopsy (FNA) and to determine the utility of MUC1 and MUC2 as markers for pancreatic ductal carcinoma. METHODS. Thirty-nine cell blocks of pancreatic FNA obtained under endoscopic ultrasound guidance were retrieved from the archives and immunostained with a monoclonal antibody directed against MUC1 and MUC2. These cell blocks were taken from 39 patients (16 females and 23 males) who had a median age of 64 years. Eleven FNAs were taken from patients with reactive/inflammatory conditions. The remaining 28 FNAs included 24 ductal carcinomas, 2 neuroendocrine tumors, 1 lymphoma sample, and 1 sarcoma sample. The presence of immunoreactivity, irrespective of the level of intensity or the percentage of cells, was considered as positive for MUC1 and MUC2 expression. Follow-up included correlation with pathology materials obtained at surgery and review of medical records. RESULTS. Twenty-three of 24 pancreatic ductal carcinomas (96%) demonstrated positive staining with MUC1. Twenty-one positive cases demonstrated either apical or diffuse membranous staining with variable cytoplasmic staining. The remaining two positive cases showed only cytoplasmic staining. One of the 11 cases of chronic pancreatitis and benign conditions demonstrated weak apical membranous MUC1 staining in the acinic cells. The difference between the two groups was statistically significant (P < 0.001, using the Fisher exact test). Three pancreatic ductal carcinomas and one chronic pancreatitis specimen demonstrated cytoplasmic staining with MUC2; the difference between the two groups was not found to be statistically significant. None of the nonductal neoplasms demonstrated expression of either MUC1 or MUC2. The sensitivity and specificity of MUC1 as a marker for pancreatic ductal carcinomas were 96% and 94%, respectively. CONCLUSIONS. MUC1 is overexpressed in pancreatic ductal carcinoma with a predominantly membranous and variable cytoplasmic staining pattern. The results of the current study suggest that the phenotypic expression of MUC1 can be used as an ancillary marker for diagnosing pancreatic ductal carcinoma in cytologic preparations. Conversely, MUC2 does not appear to be a useful marker for recognizing pancreatic ductal carcinoma in FNA specimens. © 2003 American Cancer Society.