A case of cancer of the ampulla of Vater producing alpha-fetoprotein is reported and the literature is reviewed. As far as we know, the literature contains no reports of such a case. The preoperative serum alpha-fetoprotein was remarkably high (7,480 ng/ml), but it fell to normal values (under 5.0 ng/ml) after pancreatoduodenectomy, by means of which the lesion could be radically resected. In this case, the immunohistochemical findings at optical and electron microscopy clearly indicated the production of alpha-fetoprotein by the cancer cells of the ampulla of Vater.