Chemotherapy (5-FU) with concurrent radiotherapy is recommended as an effective treatment for locally unresectable pancreatic cancer. A phase I study of S-1 with concurrent radiotherapy demonstrated promising results in late years. A 70-year-old man was revealed to have metastatic pancreatic cancer (T 4 N 3 M 1 (PER), Stage IVb). Since a curative operation was impossible in this case, he was treated with systemic chemotherapy using S-1 combined with irinotecan hydrochloride (CPT-11) as first-line chemotherapy. Because the primary lesion was increased in size after two courses,he was then treated by radiotherapy combined with S-1 as second-line treatment. S-1 (80 mg/body/day) was orally administered (2 consecutive weeks, 1-week break), and concurrent radiotherapy was performed at a daily fraction of 1.8 Gy, 5 days/week, total amount 45 Gy. Although in the early period of chemoradiotherapy, transfusion for anemia and morphine hydrochloride for pain control were necessary, his symptoms gradually improved by the reduction of primary lesion. The patient has been receiving systemic chemotherapy as an outpatient for 12 months without deterioration of quality of life.