Intraductal papillary neoplasms of the bile duct (IPN-Bs) share clinicopathologic features with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Approximately two thirds of IPMNs have activating point mutations of GNAS at codon 201. The role of GNAS mutation is unclear in IPN-B. In this study, we evaluated 41 patients diagnosed with IPN-B for clinicopathologic characteristics and follow-up information. Mutation analyses of GNAS and KRAS were performed. Twenty-three cases (56.1%) of IPN-B were categorized as the intestinal subtype, and 18 (43.9%) were considered the gastric/pancreatobiliary subtype. IPN-Bs showing intestinal differentiation demonstrated high immunohistochemical expressions of CK20, CDX2, and MUC2, as well as a significant association with macroscopic and microscopic mucin hypersecretions and villous architecture. GNAS and KRAS mutations were detected in 29% and 32% of IPN-Bs, respectively. All IPN-Bs with GNAS mutation showed intestinal differentiation. GNAS-mutated IPN-B was highly significantly associated with certain pathologic characteristics, including macroscopic and microscopic mucin hypersecretion and villous architecture. IPN-B with GNAS mutation tended to more frequently harbor KRAS mutation than those without GNAS mutation. IPN-Bs with intestinal differentiation, villous architecture, and mucin hypersecretion constitute a distinct subgroup of IPN-B, which frequently has GNAS mutation. This subtype shares common genetic alterations with IPMN of the pancreas.