We herein report two cases showing long-term complete remission (CR) in response to S-1 monotherapy. Case 1 was a 65-year-old male diagnosed with an advanced poorly differentiated adenocarcinoma of the stomach with paraaortic lymph node metastases, which disappeared after S-1 monotherapy. Subsequently a total gastrectomy was performed, and histological CR was evident. His progress is presently uneventful without recurrence 50 months after surgery. Case 2 was a 59-year-old female who underwent a total gastrectomy with a jejunal pouch. The resected tumor was a medullary type poorly differentiated adenocarcinoma infiltrating the serosa and involving the regional lymph nodes. One year after surgery, endoscopy revealed a recurrent tumor in the jejunal pouch. After the administration of S-1, this recurrent tumor completely disappeared, and she has since maintained CR for 39 months. These cases suggest that a subgroup of patients with advanced gastric cancer may attain CR with S-1 monotherapy.