Enteritis cystica profunda (ECP), an uncommon condition, is characterized by nonneoplastic cystic spaces within the wall of the small bowel. The cases of two patients who had ECP in association with Crohn's disease are reported, and the role of mucosal damage in the pathogenesis of ECP is discussed. Pathologists must recognize this entity and distinguish it from adenocarcinoma, which may arise with increased frequency in the small bowel in patients with Crohn's disease.