Fat replacement of the exocrine pancreas is a rare cause of exocrine pancreatic failure. We report two adult patients (a 25-year-old woman and a 63-year-old man) with weight loss and massive steatorrhea in whom abdominal computed tomograms were diagnostic of pancreatic lipomatosis. In both patients, oral pancreatic enzyme replacement in association with cimetidine led to a marked reduction of steatorrhea and weight gain. Pancreatic lipomatosis should be suspected in cases of severe exocrine pancreatic insufficiency in the absence of abdominal pain and diabetes. Computed tomogram scanning should lead to an increasing detection rate of this unusual condition.