A consecutive series of 36 Japanese patients with ampullary carcinoma who underwent a pancreatoduodenectomy at the Department of Surgery I, Kyushu University Hospital during the past 20 years were reviewed clinicopathologically to study prognostic factors. A univariate generalized Wilcoxon test showed that preoperative serum carcino-embryonic antigen (CEA) concentration, venous invasion, lymphatic permeation and perineural invasion were significant parameters. A multivariate Cox regression analysis showed that venous invasion was the only significant variable. In a sequential serum CEA follow up of 10 patients, an elevation of serum CEA levels was seen to correspond to the clinical development of a recurrence in six, while a high concentration of serum CEA was not evident despite the clinical manifestation of a recurrence in two, and serum CEA levels remained within the normal limits with no evidence of a recurrence in two others. According to the death certificates of 15 patients, where an exact site of metastasis was available, 11 died from liver metastasis, three from lung metastasis and one from peritoneal dissemination. These findings support the theory that a histologic invasion of the venous space is an independent prognostic factor and close attention should be paid to any signs of haematogenous metastasis, such as to the liver and lung, as well as to a serial serum CEA follow up.