A 55-year-old man with nonfunctioning islet cell carcinoma showing elevation of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels is described with genetic analyses. Pathological examination of the resected specimen revealed two independent islet cell carcinomas, one in the body and the other in the tail of the pancreas. It was proved immunohistochemically that the tumor cells, particularly those in the tail, were immunoreactive to CEA and CA 19-9 and had the property of duct cells, as well as endocrine cells. Gastrin was demonstrated immunohistochemically in these tumor cells, although its level in serum was not elevated. Genetic analyses of the fresh specimens from the tumor in the body revealed K-ras codon 12 mutation and microsatellite instability. These findings are consistent with its progressive clinical course and strongly suggest that these tumors originate, not from the islet cells of Langerhans, but from protodifferentiated cells, capable of giving rise to all the pancreatic cell types.