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The principal treatment for gastrointestinal stromal tumors (GISTs) is surgical; and complete excision is important, but cannot always be achieved. For such cases, neoadjuvant chemotherapy (NAC) with imatinib mesylate (IM) has been recommended. A case of a GIST of the second portion of the duodenum for which pancreatoduodenectomy was indicated, and for which partial resection was made possible as a result of cytoreduction by IM NAC, is reported. A 64-year-old man with pancytopenia due to hepatic cirrhosis caused by hepatitis C infection received repeated blood transfusions because of anemia of unknown origin starting 2 years earlier. Most recently, the patient had melena with hemoglobin of 5.1 mg/dL. Diagnostic imaging showed a solid tumor, 55 3 48 3 65 mm 3 , in the second portion of the duodenum showing mainly extramural development. Endoscopic aspiration biopsy showed proliferation of KIT-positive spindle-shaped heterotypic cells. GIST was diagnosed, and an exon 11 KIT mutation was found. Because of the exon 11 mutation, neoadjuvant IM was started at 400 mg/day and then eventually maintained at 300 mg/day for 10 months. Regular CT examinations showed gradual tumor shrinkage. At surgery, a tumor with strong extramural growth was found on the outer side of the duodenum that invaded the retroperitoneum. The tumor was excised as a mass, and the duodenum was resected partially. There has been no recurrence at 9 years postoperatively. Evaluating KIT exon mutations and predicting the effectiveness of NAC appear useful for determining the treatment policy for advanced GISTs.