Mixed adenoneuroendocrine carcinoma (MANEC) is defined as a tumor composed of both adenocarcinoma and neuroendocrine components. Here, we report the case of a 75-year-old woman with ampullary MANEC. She visited a physician with the chief complaint of dark urine and was diagnosed with advanced jaundice. Subsequently, she was referred to our hospital. Contrast-enhanced computed tomography scan revealed a neoplastic lesion measuring approximately 2 cm with a contrast effect at the duodenal papilla. Upper endoscopy showed a non-exposed tumor at the duodenal papilla. After biliary drainage, a subtotal stomach-preserving pancreaticoduodenectomy was performed. Histopathological examination revealed that the tumor components were composed of circular-to-oval atypical cells admixed with tubular adenocarcinoma tissue. These atypical cells were immunohistochemically positive for synaptophysin and diagnosed as neuroendocrine carcinoma with a Ki-67 labeling index of 63%. The patient was diagnosed with MANEC with a neuroendocrine carcinoma component of approximately 40%. The neuroendocrine carcinoma component had metastasized to the posterior pancreatic lymph nodes. Despite starting adjuvant chemotherapy with S-1, computed tomography revealed the presence of multiple liver metastases within 4 months after surgery. MANEC with neuroendocrine carcinoma is well known to have an extremely poor prognosis. Therefore, establishing a multidisciplinary therapy including chemotherapy is crucial.