Amyloidosis not infrequently involves the gastrointestinal tract and may result in a variety of symptoms, including those related to impaired motility, malabsorption, and ulceration due to ischemia. This report describes the case of a 74-year-old man with systemic amyloidosis secondary to multiple myeloma, with striking gross morphologic findings involving the colon, seen at autopsy, resembling severe inflammatory bowel disease. Microscopically, the small arterioles of the lamina propria were markedly narrowed or occluded by massive deposition of amyloid, presumably leading to diffuse ischemia and mucosal necrosis. Although the radiologic appearance of this condition has been well recognized, and ischemia due to amyloidosis has been described, this case is presented to demonstrate the gross anatomic changes not illustrated in previous reviews of the subject.