Ampullary adenocarcinomas have unique biologic and clinical features that result in its improved prognosis versus adenocarcinomas that arise from the distal bile ducts and pancreas. However the histological differentiation and identification of these tumors is not easily accomplished. Two abstracts at this year’s ASCO Annual Meeting describe attempts to identify unique methods for distinguishing these tumors. Abstract 4141 described a 92 gene RT-PCR assay that was used for molecular classification of patients with ampullary adenocarcinomas while abstract e15175 looked at mutational status of K-ras in patients with these tumors. The results of their abstracts will be discussed.