Segmental arterial mediolysis (SAM) is a rare non-atherosclerotic non-inflammatory vascular disease that affects mainly muscular arteries of the splanchnic and cerebral territories. Reported herein are two cases of SAM in young women with fatal outcome. One of the patients had an atypical form of the disease, which primarily affected small intestinal submucosal and subserosal arteries, and resulted in acute mesenteric ischemia. The other had bilateral brain infarction with SAM of internal carotid arteries (ICA). Pathological examination of both cases did not reveal the cause of blood flow disturbance: large mesenteric branches of the former and ICA of the latter were free of either dissection or thrombosis; in addition, small intestinal arteries of the first patient did not show signs of vasculitis. These findings suggest that unusual pathways of arterial occlusion and dissection may occur in the context of SAM.