Osteosarcoma incidence patterns suggest an aetiologic role for perinatal factors, and growth and development. Osteosarcoma patients (n = 158) and controls with benign orthopaedic conditions (n = 141) under age 40 were recruited from US orthopaedic surgery departments. Exposures were ascertained by interview, birth, and growth records. Age- and sex-adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated. Current height and age- and sex-specific height percentiles were not associated with osteosarcoma risk. Male cases, however, appeared to have an earlier adolescent growth period, and earlier attainment of final height (OR = 7.1; 95% CI = 1.6-50 for <19 vs 19+ years), whereas earlier puberty appeared protective with ORs of 0.41 (95% CI 0.18-0.89) and 0.68 (95% CI 0.31-1.5) for developing facial and pubic hair, respectively. High birth weight was associated with an elevated osteosarcoma risk (OR = 3.9; CI = 1.7-10 for 4000 g vs 3000-3500 g), although there was no trend in risk with increasing weight. These data provide some evidence that osteosarcoma is related to size at birth and in early adolescence, while earlier puberty in male subjects may be protective.