To investigate the hypothesis that survivors of pediatric solid cancer have low bone mineral density, a cross-sectional study was done of subjects who had received treatment for pediatric solid tumors before 16 years of age and were less than 40 years old at follow-up. Excluded were subjects treated for acute lymphoblastic leukemia or those who had received cranial irradiation, total body radiation, or nonautologous bone marrow transplant. The study group consisted of 38 subjects, with the most common diagnoses being lymphoma (n = 17), sarcoma (n = 8), Wilms tumor (n = 5), and neuroblastoma (n = 4). Median age was 22 years (range 12-32). Time from diagnosis of underlying cancer averaged 12.6 years (range 5.5-20.3). Using criteria of osteopenia (Z-score < or = -1.0 and > -2.0) and osteoporosis (Z-score < or = -2.0) for any one or more areas including total body, lumbar spine, total hip, or femoral neck density, 13 of the 38 subjects (34%) had osteopenia or osteoporosis. A further six subjects (16%) had isolated upper extremity osteopenia or osteoporosis. Multivariate analysis showed a direct relationship between the number of chemotherapy drugs administered and the presence of osteopenia or osteoporosis in the lower extremities (P = 0.03). Young survivors of childhood solid tumors are at increased risk of developing premature osteopenia or osteoporosis, and screening evaluations and follow-up are warranted.