We conducted a pilot study using S-1 (TS-1), a novel oral derivative of 5-fluorouracil, as neoadjuvant chemotherapy for potentially resectable scirrhous gastric cancer. The neoadjuvant chemotherapy consisted of two courses (each, 4-week administration and 2-week withdrawal) of S-1 at 100-120 mg/body per day. Five patients were enrolled in this pilot study and underwent resection. The response rate for the neoadjuvant chemotherapy was 60% (three partial response [PR]; two stable disease [SD]). Three of the five patients received curative resection; the other two patients received noncurative resection because of localized peritoneal dissemination and positive results on cytological examination of the abdominal washing. No toxicity of grade 3 or more was exhibited during the two courses of chemotherapy. Pathological examination of the resected specimens revealed a marked reduction in the distribution of viable cancer cells in the stomach in the three patients with PR. In one of these patients, pathological findings suggestive of the possibility of disappearance of the cancer cells in the perigastric and paraaortic lymph nodes were noted. Because of the unexpectedly high response to S-1, we consider that the efficacy of S-1 as neoadjuvant chemotherapy for scirrhous gastric cancer should be verified by phase II and III trials.