We report 2 patients with an unusual form of chronic pancreatitis, both of whom were treated for clinical suspicion of pancreatic malignancy. The surgical specimens revealed a dense lymphoplasmacytic infiltration of the main and interlobular branches of the pancreatic duct, causing sclerosis of the duct wall, diffuse irregular lumenal narrowing, extensive parenchymal fibrosis, and organ enlargement. Neither case showed calcifications, fat necrosis, or cyst formation, features usually seen in alcoholic pancreatitis, nor was there any evidence of neoplasia. One patient had an unusual form of acalculous cholecystitis, but without cystic duct inflammation or fibrosis. Both patients recovered well from the surgical procedure and have not had any complications or relapse of their symptoms. To the best of our knowledge, these cases are representative of the recently described non-alcoholic duct destructive chronic pancreatitis, which is thought to be immune-mediated.