Major duodenal papilla cancer (MDPC) represents the primary type of duodenal cancer, and is typically considered a periampullary carcinoma as most tumors arise in this region. This report describes an extremely rare case involving a patient with rapidly and extensively recurrent MDPC following pancreaticoduodenectomy, who achieved complete response by concurrent image-guided radiation and intravenous oxaliplatin plus oral capecitabine therapies. The patient was a 50-year-old female who was admitted to our hospital 6 wk after resection for MDPC for evaluation of a nontender and enlarged node in the left side of her neck. After clinical work-up, the patient was diagnosed with postoperatively recurrent MDPC with widespread lymph node metastases at the bilateral cervix, mediastinum, abdominal cavity, and retroperitoneal area. She was administered whole field image-guided radiation therapy along with four cycles of the intravenous oxaliplatin plus oral capecitabine regimen. A complete response by positron emission tomography with 18-fluorodeoxyglucose was observed 4 months after treatment. The patient continues to be disease-free 2 years after the diagnosis of recurrence.