Data on the risk factors for typhlitis in children with cancer are limited. The aim of the study was to define the epidemiologic and clinical features of typhlitis and to elucidate predisposing factors for its development. The medical records of pediatric patients with cancer who were diagnosed with typhlitis from 1995 to 2005 were reviewed for clinical, laboratory, and imaging findings. The results were compared with a group of patients with cancer but without typhlitis who were hospitalized during the same period. Of the 843 cancer patients, 42 (5%) had episodes of typhlitis; 32 of them (76%) were being treated for hematologic malignancies. The incidence was highest in patients with Burkitt's lymphoma (15%) and acute myeloblastic leukemia (12%). Work-up included abdominal x-ray in all patients; abdominal ultrasonography and computed tomography were performed in 23% and 11% of patients, respectively. No cases were missed by plain x-ray when compared with computed tomography and ultrasonography. The typhlitis was treated without surgery and survival was 100%. On multivariate analysis, mucositis [odds ratio (OR) = 30.7], stem cell transplantation (OR = 58.9), and receipt of chemotherapy in the previous 2 weeks (OR = 12.9) were significantly associated with the occurrence of typhlitis. We conclude that most children with typhlitis may be treated without surgery in most cases with favorable outcome. A high index of suspicion may be warranted in patients after stem cell transplantation or chemotherapy and patients with mucositis.