Of 103 patients with high-grade osteosarcoma, 27% had tumours localized outside the extremities. Non-extremity patients were significantly older at diagnosis than patients with extremity tumours (median 38 vs. 17 years). More than 90% of patients with extremity tumours received adequate treatment (aggressive chemotherapy plus at least marginal surgery), compared with only 25% of patients with non-extremity tumours. Failure of adequate treatment was due to inoperable tumour, intralesional surgery and age preventing aggressive chemotherapy. There was a highly significant difference in both local tumour control and overall survival, both favouring patients with extremity tumours. Within the extremity tumour group, patients who were treated in prospective multicentre trials had a significantly better outcome than non-trial patients. Our results show that the fraction of patients with high-grade tumours that fall outside trials designed for 'classical osteosarcoma' may be larger than is usually acknowledged, and that the results reported for the classical group are by no means representative of the whole patient population. Improved and new treatment approaches are needed for patients with non-extremity tumours, particularly in the older age groups.