Combination chemotherapy with S-1 and gemcitabine(GEM)was given to patients with advanced pancreatic cancer and favorable results were obtained. These patients were 77-(Stage IVa), 68-(Stage IVb), and 64-year-old males (Stage IVb). They were administered S-1 at a dose of 80-100 mg/day for 2 weeks and GEM at a dose of 1,000-1,200 mg/body on days 8 and 15 followed by a 2-week recovery period. One course consisted of a 2-week treatment period and a recovery period; this course was repeated in all of these patients. The 3 types of patients have survived for a year and five months, a year and three months, and nine months, respectively, after diagnosis. In the first patient, who was in Stage IVa, the primary cancer has been maintained in a reduced state without metastasis. In the other two patients, who were in Stage IVb, the primary cancer and hepatic metastatic lesions have been reduced remarkably. Quality of life is good in all the patients. Combination therapy with S-1 and GEM can be provided for a long-term treatment with few adverse reactions on an outpatient basis. Based on the changes in tumor markers, we observed that the inhibitory effects of this combination chemotherapy are immediate and persistent with long-term treatment. Therefore, we expect S-1/GEM combination therapy to be the chemotherapy of choice for advanced pancreatic cancer.