BACKGROUND Patients with gastric cancers producing alpha-fetoprotein (AFP) were reported to have a poor prognosis with high rates of liver metastasis. The purpose of the present study was to clarify the clinicopathological features of AFP-producing gastric cancers, in particular characteristics of liver metastasis, and to evaluate treatment of these cancers. METHODS In 27 of the 29 cases with elevated preoperative serum AFP levels among a total of 974 primary gastric cancers, AFP production was confirmed in gastric cancer cells by immunohistochemistry. These cases were included in the AFP-positive gastric cancer group (AFP(+), 2.7%). The remaining 945 cases with normal serum AFP levels were designated the AFP-negative gastric cancer group (AFP(-)). RESULTS There was a higher incidence of lymph node metastasis, a deeper invasion of the gastric wall, a higher frequency of advanced stage, a more marked lymphatic invasion and a higher rate of liver metastasis in the AFP(+) group than in the AFP(-) group. The patients received curative resection in AFP(+) group had a significantly worse survival rates in comparison to that in AFP(-) group. With respect to liver metastasis (n = 17) in AFP(+) group, of 3 cases who received curative hepatic resection, 1 patient survived more than 3 years, while the remaining 2 died in less than 3 years due to multiple liver recurrence. The patients (n = 5) who received palliative resection for liver metastasis followed by transarterial continuous infusion chemotherapy all died in less than 1 year. CONCLUSIONS AFP-producing gastric cancers had aggressive behavior and their clinical or biological features were quite different from the common AFP-negative gastric cancers. Surgical resection of liver metastasis from AFP-producing gastric cancers was unsatisfactory. The development of a novel multimodal therapy against AFP-producing gastric cancers is needed.