Intraductal papillary mucinous neoplasm (IPMN) is a well-established entity in pancreatic neoplasms and a precursor of infiltrating adenocarcinoma. Fascin, an actin-bundling protein involved in cellular motility, is upregulated in many human neoplasms. Its overexpression in pancreatic intraepithelial neoplasia, a precancerous lesion sharing many characteristics with IPMN, has been reported. However, fascin expression in IPMN remains unknown. The aim of this study was to investigate fascin expression in IPMNs and to elucidate its relationship to clinicopathological features, including histological grade and phenotypic subclassification. We evaluated fascin expression by immunohistochemistry in 116 surgical specimens, followed by quantitative analysis of fascin mRNA expression using a laser microdissection system and real-time reverse-transcriptase polymerase chain reaction in eight frozen samples. Fascin expression was significantly higher in borderline neoplasms (25/29, 86%) and carcinomas (37/42, 88%) than in adenomas (23/45, 51%) (Po0.05, respectively), but no difference was observed between borderline neoplasms and carcinomas. With regard to the subclassification, intestinal-type neoplasms (35/39, 90%) were more frequently positive for fascin than gastric-type neoplasms (36/59, 61%) (Po0.05). Two oncocytic-type neoplasms were both fascin-negative. Fascin mRNA expression seemed to be higher in moderately to severely dysplastic epithelium than in mildly dysplastic epithelium (not statistically significant), supporting the immunohistochemical experiments. Our findings suggest that fascin overexpression is involved in the progression of IPMN. Keywords: intraductal papillary mucinous neoplasm; fascin; immunohistochemistry; laser microdissection; realtime RT-PCR; phenotypic subclassification Intraductal papillary mucinous neoplasm (IPMN) is a well-established entity in pancreatic neoplasms. It was first reported in 1982 as a special type of pancreatic neoplasm with a characteristic endoscopic finding of extrusion of mucin through the ampulla of Vater. 1 At present, the term is used to unify tumors characterized by intraductal proliferation of neoplastic mucinous epithelium, which usually forms papillae and leads to cystic dilation of the pancreatic ducts. 2,3 Because IPMNs show a broad spectrum of dysplasia ranging from adenoma and borderline neoplasm to carcinoma in situ, the existence of an adenoma-carcinoma sequence is probable. In addition, some IPMNs are associated with infiltrating adenocarcinoma. Therefore, IPMN is gaining attention as a precursor of infiltrating adenocarcinoma in the pancreas as well as pancreatic intraepithelial neoplasia (PanIN). [4][5][6] Investigation of factors correlated with the progression of noninvasive and/or invasive IPMNs is important.