Chronic granulomatous disease (CGD) is a primary phagocytic disorder characterized by greatly increased susceptibility to severe bacterial and fungal infections. Patients with CGD may have gastrointestinal manifestations, commonly colitis, usually mimicking Crohn disease. We report an adult case, the second in literature, of CGD with severe colitis displaying histologic features of ulcerative colitis. The patient had a prompt improvement (continuing up to more than 5 y of follow-up) of the clinical picture after ileostomy and fecal diversion.