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We further characterize the heterogeneous carcinomas of the papilla of Vater (CPVs) in relation to various clinicopathologic patient characteristics and patient survival.Of the 71 reevaluated CPVs, 32 were intestinal, 26 were pancreatobiliary, 6 were mixed, 4 were mucinous, and 3 were poorly differentiated carcinomas. The prevalence of cytokeratin 20 and cytokeratin 7 correlated with the intestinal (25/32 [78%] vs 13/32 [41%]) and pancreatobiliary (6/26 [23%] vs 24/26 [92%]) phenotypes. CDX2 was found in mucinous (3/4 [75%]), intestinal (7/32 [22%]), and some mixed (1/6 [1%]) CPVs. A KRAS mutation was detected in all poorly differentiated CPVs and in about 20% of each of the other types. In multivariate analyses, tumor type, local tumor spread, and lymph node metastases were independent prognostic factors of patient survival.We provide further evidence of the prognostic relevance of the phenotypic and genotypic diversity of CPVs. Besides the poorly differentiated CPV, the most common KRAS wild type makes them a putative target for an anti–epidermal growth factor receptor therapy.