Desmoplasia is a common feature of infiltrating ductal adenocarcinoma of the pancreas. This process is intricately interacted between the host and neoplastic cells. Recently, by transcriptome analysis, periostin was identified as a significantly highly expressed gene in pancreatic stellate cells. To investigate the characteristics of periostin immunodeposition in pancreatic ductal neoplasms, we performed immunohistochemistry and in situ hybridization, focusing on tumor-stromal cells interactions. Eighty-one surgically resected pancreatic lesions, including 35 pancreatic ductal adenocarcinoma, 26 intraductal papillary-mucinous neoplasms, 11 mucinous cystic neoplasms and 9 chronic pancreatitis, were studied. In all ductal adenocarcinomas, periostin deposition was observed in the stroma around the infiltrating cancer on immunohistochemistry. Cellular stroma of mucinous cystic neoplasm, called 'ovarian-type' stroma, did not show periostin deposition. In chronic pancreatitis, most of the staining patterns of periostin were perilobular and meshwork-like. Periostin gene expression was detected solely in the stromal cells on in situ hybridization. Intraductal papillary-mucinous neoplasms were classified into four groups on the basis of the histological grade, namely, adenoma, non-invasive adenocarcinoma, adenocarcinoma with microscopical invasion and with macroscopically evident invasion. In intraductal papillary-mucinous neoplasm, periostin deposition in the periductal stroma increased in frequency and intensity in adenocarcinoma compared with adenomas (P=0.014). Furthermore, our results showed that a higher frequency of periostin deposition was correlated with a higher frequency of 'intestinal phenotype' of proliferating epithelium (P=0.036) and laminin-5gamma2 chain expression (P<0.001) in intraductal papillary-mucinous neoplasm, the latter of which is frequently expressed in invasive carcinoma. This is the first report to describe the periostin immunohistochemistry in intraductal papillary mucinous neoplasm of the pancreas.