Mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumour of the gastrointestinal tract with both epithelial and neuroendocrine components. We describe a case of a 57-year-old man who presented with yellow sclera and dark urine. Contrast-enhanced computed tomography (CT) showed enlargement of the intra and extrahepatic bile ducts and a neoplastic lesion at the end of the common bile duct which was indistinguishable from the adjacent head of the pancreas and duodenum. A pancreaticoduodenectomy was performed and histopathological examination of resected samples showed that tumour was a complex lesion with adenocarcinoma and neuroendocrine components positive for neuroendocrine markers (chromogranin A and synaptophysin) with a Ki-67 labelling index of 40%. The patient was diagnosed with MANEC in the ampulla of Vater with a neuroendocrine carcinoma component of approximately 70%. Ampullary MANECs are highly aggressive tumours with a high risk for distant metastases and a poor prognosis. Therefore, establishing a standard therapeutic strategy is crucial.