Gastrointestinal (GI) manifestations of leukemia occur in up to 25% of patients at autopsy, generally during relapse. Its presence varies with the type of leukemia and has been decreasing over time due to improved chemotherapy. Gross leukemic lesions are most common in the stomach, ileum, and proximal colon. Leukemia in the esophagus and stomach includes hemorrhagic lesions from petechiae to ulcers, leukemic infiltrates, pseudomembranous esophagitis, and fungal esophagitis. Lesions in the small and large bowel are usually hemorrhagic or infiltrative. Infiltration of lymphoreticular organs, mainly spleen, liver, and lymph nodes, is more prominent in chronic than acute leukemia. Neutropenic enterocolitis, a necrotizing process involving the cecum, ascending colon, and terminal ileum, is increasing in incidence due to greater intensity of chemotherapy. Distension of bowel leads to mucosal breaches, permitting entry of organisms that grow profusely in the absence of neutrophils. Ischemic necrosis follows, leading to perforation and/or peritonitis. Patients present with fever, abdominal pain, diarrhea, nausea, vomiting, abdominal distension and tenderness. Ultrasound and computed tomography scans show thickening of the bowel wall. Treatment is supportive with surgery for necrosis and perforation. The main GI causes of death in leukemia are hemorrhage, infection, and necrotizing enterocolitis.