Large cell neuroendocrine carcinoma in the ampulla of Vater is rare and very different from the common ampullary adenocarcinoma. A 59-year-old man was admitted with obstructive jaundice. Gastroendoscopy showed a swollen ampulla of Vater and pathological examination of an ampullary biopsy revealed findings of a carcinoid tumor. After endoscopic biliary drainage, he underwent pancreaticoduodenectomy. A diagnosis of large cell neuroendocrine carcinoma was confirmed by immunohistochemical examination of the resected specimen. Despite adjuvant chemotherapy with cyclophosphamide and cisplatin, liver and peritoneal metastasis developed within 5 months and he survived for only 10 months after the operation. Thus, further investigations are needed to find a more effective postoperative adjuvant chemotherapy agent to treat patients with this aggressive tumor.