A 65-year-old man was referred to our hospital with a primary complaint of unintentional weight loss. Upper gastrointestinal endoscopy showed a large duodenal tumor, and computed tomography (CT) showed tumor invasion of the pancreatic head, associated with lymph node swelling around the tumor and abdominal aorta. After 4 courses of chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6), follow-up upper gastrointestinal endoscopy and biopsy showed no evidence of a duodenal tumor. However, follow-up CT showed persistent lymph node swelling near the superior mesenteric artery. The patient therefore underwent pancreaticoduodenectomy with curative intent. At 18 months after the surgery, there were no findings suggestive of tumor recurrence.