Although neoadjuvant chemotherapy has been recognized as an important option to improve the clinical outcome of patients with advanced gastric carcinoma, the precise histological effects of neoadjuvant chemotherapy on the primary and metastatic foci have not well been documented. The aim of the present study was thus to evaluate histological effects of S-1-based neoadjuvant chemotherapy on the resected specimens of gastric carcinoma and regional lymph nodes, and primarily to focus on the histology of the cases showing complete regression of the primary cancer cells. A total of 164 patients received neoadjuvant chemotherapy with the combination of S-1 (80 to 120 mg/body/day for 3 weeks) and cisplatin (35 to 60 mg/m2 on day 8). One course of the regimen was completed in 5 weeks and the next course was started after 2 weeks. A total of 9 patients who showed complete regression of the primary gastric cancer were subjects of the study. A total of 77 cases (46.9%) responded to the neoadjuvant chemotherapy and 9 cases (5.5%) showed a complete regression of the primary gastric carcinoma. Three out of 9 cases had remnant cancer cells in the metastatic foci; 1 in the liver and 2 in the regional lymph nodes. Five of 9 cases were solid-type poorly-differentiated adenocarcinoma (por1), and the incidence of responders was the highest in patients with por1. A total of 8 cases were alive and the mean postoperative survival was 612±192 days. One patient died 518 days after gastrectomy associated with hepatic resection. S-1-based neoadjuvant chemotherapy has significant histological effects on gastric carcinoma and metastatic foci, which may further improve long-term clinical outcome in patients with advanced gastric carcinoma.