There are numerous reports on the mixed cellular population of primary tumors, especially in the gastrointestinal tract. However, reports of mixed cellular population in metastatic foci are rare. This is a report of a case of periampullary papillary adenocarcinoma of the duodenum with 4 types of cellular population. Metastases to the regional lymph nodes also contained 4 different cell types. The histogenesis of the mixed cellular population in the primary tumor and theories proposed to explain the pathophysiologic mechanisms of mixed cellular population in the metastatic foci are discussed.