Data on 715 Japanese patients with gastric cancer were studied retrospectively with regard to the relationship between macroscopic and microscopic diagnoses of serosal invasion and clinicopathological factors affecting the accuracy of the macroscopic diagnosis. Although there was no macroscopic evidence of serosal invasion intraoperatively (S0 or S1), there was histological evidence of cancer cells on the serosal surface in 69 patients (9.7%). In these serosal invasion-positive cases, the tumors were larger; were located more commonly in the upper third, lesser and greater curvatures of the stomach; were Borrmann type 3 or type 4 tumors, and of an undifferentiated histologic type with an infiltrative growth pattern more commonly, and had more extensive lymphatic and vascular vessel invasion and lymph node metastasis (P < 0.01). Total gastrectomy was done more often for the serosal invasion-positive group, but the extent of lymph node dissection was comparable. Cases of a noncurative resection because of a positive surgical margin were more frequent in the serosal invasion-positive group (8/69 vs. 14/646, P < 0.01), and most had undifferentiated and infiltrative cancers. The 10-year survival rates were 49.2% and 85.5% for patients with and without serosa invasion, respectively. These findings clearly show that the serosal surface, especially in cases of the undifferentiated or infiltrative type of gastric cancer, must be closely inspected intraoperatively.