The variety and distribution of skeletal pathology in children with acute lymphoblastic leukemia rarely seen in other disease states. Skeletal radiographic changes associated with and/or suggestive of acute leukemia include diffuse osteopenia, metaphyseal bands, periosteal new bone formation, geographic lytic lesions, sclerosis, mixed sclerosis/lysis, and permeative destruction. This retrospective analysis of 83 children with acute lymphoblastic leukemia suggests that children without radiographic skeletal abnormalities have an “aggressive” form of leukemia. Children with one to four lesions have an “indolent” form of leukemia that is of short duration. Children with five or more lesions have an indolent form of leukemia that is of longer duration. The longer duration of symptoms before diagnosis reduces the survival rate to that of the aggressive form of leukemia. It is therefore imperative that physicians who treat children recognize the orthopaedic/radiographic manifestations of acute leukemia (the most common pediatric malignancy) to facilitate diagnosis, and, thereby, improve survival.