The association between pancreatic panniculitis and pancreatic disease is well described, but differentiation among the neoplastic causes of the syndrome remains difficult due to substantial overlap in histological and immunohistochemical features. We report a case of subcutaneous fat necrosis as the presenting feature in a 61-year-old man with metastatic carcinoma of pancreatic origin. Previous pathological evaluation of the patient's liver biopsy led to an initial diagnosis of adenocarcinoma of unknown primary site. One month later, the patient presented with pancreatic panniculitis, prompting further investigation. Immunohistochemistry was consistent with neuroendocrine differentiation, but the patient rapidly decompensated and died before the evaluation was complete, leaving the definitive diagnosis in question. In our review of the published reports of tumor types associated with pancreatic panniculitis, we found that immunohistochemical staining and electron microscopy can and should be used in conjunction with clinical correlation to accurately differentiate neuroendocrine tumors from carcinomas with acinar cell features. Accurate diagnosis of these tumors is necessary to determine prognosis and define appropriate therapy.