Context.-Intraductal tubulopapillary neoplasm (ITPN)is a rare intraductal epithelial neoplasm of the pancreas recently recognized as a distinct entity by the World Health Organization classification in 2010. It is defined as an intraductal, grossly visible, tubule-forming epithelial neoplasm with high-grade dysplasia and ductal differentiation without overt production of mucin. The diagnosis can be challenging owing to morphologic overlap with other intraductal lesions and its rarity. While recent advances in molecular genetic studies of ITPN have provided new tools to facilitate clinical diagnosis, the limited number of cases has yielded limited follow-up data to guide management.Objective.-To provide a clinical, pathologic, and molecular update on ITPN with respect to clinical presentation, imaging findings, histopathologic features, differential diagnosis, biological behavior, molecular characteristics, and treatment options.Data Sources.-Analysis of the pertinent literature (PubMed) and authors' research and clinical practice experience based on institutional and consultation materials.Conclusions.-Clinical presentation, imaging findings, histopathology, immunohistochemistry studies, molecular characteristics, prognosis, and treatment options of ITPN are reviewed. Important differential diagnoses with other intraductal neoplasms of the pancreas-especially intraductal papillary mucinous neoplasm-using histopathologic, molecular, and immunohistochemical studies, are discussed. Despite the recent progress, more studies are necessary to assess the biology and genetics of ITPN for a better understanding of the prognostic factors and treatment options.(Arch Pathol Lab Med. 2016;140:1068-1073; doi: 10.5858/arpa.2016-0207-RA) T he intraductal neoplasms of the pancreas are defined by the current 4th edition of the World Health Organization (WHO) classification as macroscopic epithelial neoplasms with ductal differentiation that grow in the pancreatic ductal system. The 2 entities included in this category are intraductal papillary mucinous neoplasm (IPMN) and intraductal tubulopapillary neoplasm (ITPN). Note that intraductal lesions with nonductal differentiation, such as acinar cell carcinoma, are not included in this category. Interestingly, before the current WHO classification, intraductal neoplasms of the pancreas were classified into 3 groups: IPMN, pancreatic intraepithelial neoplasia (PanIN), and intraductal tubular neoplasm.1,2 Intraductal tubular neoplasm was then further classified into intraductal tubular adenoma and intraductal tubular carcinoma, with intraductal tubular adenoma considered as the precursor of intraductal tubular carcinoma.3 Both IPMN and ITPN can be either cystic or solid-mass forming. The distinction between the intraductal neoplasms and PanIN is that PanIN is microscopic. On the contrary, by definition, both IPMN and ITPN are grossly and radiographically detectable lesions with an arbitrary minimal size criterion of 1 cm. Intraductal tubulopapillary neoplasms can have variable componen...