A 78-year-old male patient with a history of the right hemicolectomy due to the adenocarcinoma was admitted by the com-plaint of epigastric discomfort. Laboratory data showed an increase in liver biochemistries (aspartate aminotransferase (AST): 159 IU/L, alanine aminotransferase (ALT):235 IU/L, alkaline phosphatase (ALP): 350 IU/L, gamma-glutamyl transferase (GGT): 911 IU/L, total bilirubin: 1.55 mg/dl and direct bilirubin: 0.82 mg/dl). Endoscopic retrograde cholangiopancreatiogra-phy (ERCP) administered after the gastrointestinal (GI) upper endoscopy was compatible with the tumoral lesion, and biopsy confirmed ‘neuroendocrine carcinoma’. Pylorus-preserving pancreaticoduodenectomy (PPPD) was performed with R0 resec-tion. Pathologic evaluation revealed a 1,5 cm tumor of large cell neuroendocrine carcinoma (LCNEC). Five months later, biopsy of suspicious lesions in the liver was documented as ‘high-grade neuroendocrine carcinoma metastasis’. He was referred to the oncology for chemotherapy, but, unfortunately, he expired three months later. Large cell neuroendocrine carcinoma (LCNECs) of the ampulla of Vater might have an aggressive clinical course despite radical resections involving lymph node dissections. Small tumor size and lymph node negativity are not reliable factors for this tumor type.