Early identification of acute pancreatitis etiology is essential for choosing the best therapeutic management. The main causes are cholelithiasis and alcohol consumption. Tumors that obstruct the main pancreatic duct are uncommon causes of acute pancreatitis. Duodenal neuroendocrine tumors are rare entities and may be exceptional causes of acute pancreatitis. A 57-year-old male, with associated severe cardiovascular pathology, was admitted with clinical and biological picture of acute pancreatitis. Biliary and alcoholic causes were excluded. Abdominal contrast-enhanced computed tomography scan identified circumferential wall thickening of the second segment of the duodenum with peri-ampullary and papillary nodular non-homogenous contrast enhancement aspect. Upper gastrointestinal endoscopy described irregular hypertrophic duodenal mucosal folds and biopsies were performed. The histopathological diagnosis after immunohistochemistry tests was duodenal large-cell neuroendocrine carcinoma. The patient was referred to the oncology clinic and palliative treatment was initiated. The evolution was marked by additional complications due to the tumor evolution - upper gastrointestinal bleeding and obstructive jaundice, conservatory treated and, respectively, by interventional radiology technique. This case illustrates that, although often obvious, etiological diagnosis approach of acute pancreatitis can be sometimes challenging. Tumor cause is infrequent and requires thorough work-up, as the treatment is different. Although extremely rare and sometimes with mild clinical presentation, duodenal neuroendocrine carcinomas may have dramatic onset and evolution, involving extensive therapeutic resources.