Pancreatic panniculitis represents a rare dermatological manifestation mainly due to a pancreatic disorder, but other etiologies are possible. Even rarer, it can occur prior to the clinical signs of the underlying disease, and its presence must orientate the investigations especially towards pancreas, liver and neuroendocrine system. We report a rare case of a 47-year-old male patient who presented to the Emergency Unit complaining about a two weeks-long-persistent pain in the upper abdomen and biliary vomiting. The medical history included alcohol abuse. Several days prior to the onset of these symptoms, the patient has noticed the occurrence of a nodular inflammatory lesion of 5∕3 cm on the right calf (this makes the case even rarer). Based on clinical aspect and high levels of pancreatic enzymes, acute pancreatitis was diagnosed. Contrast-enhanced abdominal computed tomography (CT) revealed a cystic pancreatic mass and dilated intrahepatic biliary ducts. Abdominal magnetic resonance imaging (MRI) revealed a cystic tumor of the pancreatic head and thrombosis of the portal vein, which increased the suspicion of pancreatic adenocarcinoma. Biopsy was performed from the calf nodular lesion, with the diagnosis of panniculitis. This case, besides its rarity, supports the clinical important value of a pancreatic workup in case of histologically proved panniculitis, even without pancreatic related symptoms.