A 52-year-old woman visited our hospital with epigastralgia. Detailed examination revealed a duodenal cancer of the ascending limbs. Since she refused the resection, the administration of S-1 alone was commenced. After one course of this treatment, oral intake became impossible. Duodenography and endoscopy showed duodenal obstruction, and she underwent surgery. The tumor proved to be unresectable due to direct invasion of the inferior vena cava. Duodenojejunostomy was performed. After surgery, she was treated by S-1 and survived 2 years and 11 months, which resulted in 3 years and 2 months' long survival from her first visit. The intervals of the intake and home stay, after the operation, were 2 years and 8 months and 2 years and 5 months, respectively. The combination of S-1 administration and bypass operation provides a useful alternative for the treatment of unresectable duodenal cancer with stenosis.