The purpose of this study was to compare histologic subtype and growth pattern, including invasion and intraductal spread to branch ducts, in main duct-type intraductal papillary-mucinous carcinoma (IPMC) by histopathology and immunohistochemistry. Five surgically resected samples of main duct-type IPMC from five patients, were studied. Main lesions, invasive components, and adjacent secondary ducts were examined microscopically. We performed immunohistochemistry with monoclonal mucin 2 (MUC2) and polyclonal orotate phosphoribosyltransferase (OPRT) antibodies. Three cases showed adenoma components in the main duct. Two of these showed intestinal-type accompanied by intraductal spread to branch ducts, neoplastic changes in branch ducts consisting of high-grade pancreatic intraepithelial neoplasia-like ducts positive for MUC2, and ducts filled with arborizing neoplastic cells, resembling pancreatobiliary type. The other case showed gastric-type adenoma and intestinal-type carcinoma in situ (CIS) in the main duct, with minimal tubular invasion. The two remaining cases showed no adenoma components in the main duct, but showed abrupt transition from normal epithelium to CIS (pancreatobiliary type or oncocytic type) and massive invasion diffusely positive for OPRT. These results suggest that IPMC with adenoma components in the main duct undergoes intraductal spread to branch ducts and has low malignant potential. The progression of one subtype to another is associated with intraductal spread of intraductal papillary-mucinous neoplasm (IPMN). However, IPMC without adenoma components is associated with marked invasion.