Prognostic factors of gastric cancer with positive serosal invasion and regional lymph node metastasis were evaluated by multivariate analysis. Sixty-seven patients with the T3N1M0 subgroup of stage IIIA disease were evaluated, in which 34.9 +/- 13.4 nodes were dissected in extended lymph node dissection, and 6.5 +/- 6.2 were metastatic. Routine postoperative systemic chemotherapy with mitomycin C and N1-(2'-tetrahydrofuryl)-5-fluorouracil was administered. With this approach, the 5-year survival rate of stage IIIA disease was 47.6%. By Cox proportional hazards model, diameter of serosal invasion was the only significant determinant of prognosis in the T3N1M0 subgroup. The predicted 5-year survival rate for 24 patients with serosal invasion less than 3.0 cm in diameter was 59.5%, compared with 11.5% for 38 patients with invasion of 3.0 cm or larger in diameter. The number of metastatic nodes and the type of operation (total gastrectomy or less than total gastrectomy) did not affect the prognosis. When gastric cancer has both positive serosal invasion and metastatic regional lymph nodes, the diameter of serosal invasion is the more important factor for predicting prognosis.