From January 1986 to March 1993, 29 patients aged between 40 and 60 years with primary high grade osteosarcoma of the extremity were treated at Rizzoli Institute with neoadjuvant chemotherapy. Before surgery patients received cisplatin and adriamycin. Postoperatively, patients with a good histologic response received the same two drugs preoperatively used, while in case of poor response ifosfamide and etoposide were added to cisplatin and adriamycin. Twenty-five patients (86%) were surgically treated with a limb salvage, whereas 4 patients (14%) were amputated. With a median follow-up of 8 years (5-12), the 8-year event-free survival was 57% and the 8-year overall survival was 62%. No chemotherapy-related deaths were recorded and toxicity was manageable. These results are significantly better than those achieved in 24 patients of the same age, treated at Rizzoli Institute between 1975 and 1985 only with surgery (87% of amputation and 17% of 8-year event-free and overall survival) and indicate an advantage for the use of neo-adjuvant chemotherapy also in patients with high grade osteosarcoma of the extremity older than 40 years.