Our data clearly revealed and confirmed that biliary and pancreatic ITPNs generally lack KRAS and GNAS mutations, a remarkable finding given the crucial role of KRAS in the carcinogenesis of PDAC (mutated in >90% of cases), its precursor lesions (e.g., IPMN) and CCA (mutated in 17% of cases), and recurrent GNAS mutations in pancreatic IPMNs. Here, GNAS is linked to pancreatic intraductal papillary-mucinous neoplasm.