Objective: To investigate the clinicopathologic features, and differential diagnosis and treatment method of the mixed acinar-neuroendocrine carcinoma (MANEC) of the pancreas. Methods: The clinical record of one patient with MANEC was retrospectively analyzed, in combination with domestic and foreign literature review, to summarize the clinical features, pathological features, differential diagnosis and treatment method for this disease. Results: Preoperative imaging examinations suggested that the patient had a tumor of descending duodenum, and then the patient underwent surgical treatment. The pathological diagnosis was pancreatic MANEC. The patient was discharged after operation and no tumor recurrence or metastasis was noted 20 months later. Conclusion: MANEC of the pancreas is extremely rare, usually without typical symptoms, and the final diagnosis depends on pathological findings. Its prognosis remains unclear to date, but early surgical treatment can significantly improve the overall survival.