The preponderance of pancreatic tumors is adenocarcinoma of the ductal type; carcinomas with multiple lineage differentiation are extremely rare. We report an unusual case of pancreatic carcinoma with combined acinar and neuroendocrine differentiation and minor ductal component with concurrent acinar-ductal metaplasia (ADM), an early lesion implicated in ductal carcinogenesis. The patient is a 56-year-old man with vague complaints of dull left upper quadrant pain with radiation across the mid-portion of his abdomen. A computer tomography scan revealed an irregular enlargement of the distal 3.2 cm of the pancreatic body. A distal pancreatectomy was then performed. Histologic examination revealed a pancreatic carcinoma with cellular features of eosinophilic granular cytoplasm and salt-pepper nuclei. The acinar differentiation of the carcinoma was confirmed by positivity on periodic acid-Schiff stain resistant to diastase digestion (dPAS), positivity for antitrypsin on immunohistochemistry (IHC), and presence of zymogen granules on electron microscopy (EM). The neuroendocrine differentiation was evident by positive synaptophysin and chromogranin stain on IHC and neuroendocrine granules on EM. The ductal component was only visible by PAS stain and immunostains for CEA and CK19A and accompanied by a number of the acinar-ductal metaplasia lesions adjacent to the main tumor. Thus, the histological, histochemical, immunohistochemical and electron-microscopic evidence all suggested that the pancreatic carcinoma underwent trilineage differentiation.