Primary high-grade intramedullary osteosarcoma of the extremities is a clinically aggressive bone tumour. There is an ongoing effort to further improve efficacy of neo-adjuvant chemotherapy and reduce chemotoxicity by trying to identify osteosarcoma patients who are at risk of treatment failure as well as to identify those who can do with less chemotherapy. In only 5% of patients, first distant metastasis or local relapse occurs 5 years or more after initial treatment for osteosarcoma. Patients and physicians can therefore easily erroneously consider a patient with osteosarcoma cured if he or she is disease-free for more than 5 years following diagnosis and treatment. To investigate if these rare late relapsing patients are characterised by specific clinico-pathological features, we examined clinical and histological variables of late relapse (first local recurrence or metastasis 5 years or more after initial diagnosis) out of a total of 2,243 patients, with a special interest in the histological osteosarcoma subtype. In total, 33 patients had a documented relapse 5 years or more after diagnosis. Half of the patients had good response (>or=90% necrosis) to pre-operative chemotherapy and the other half a poor response (<90% necrosis) and late relapses seemed to be more frequently proportionately in those who had a good initial response to chemotherapy. The occurrence of late relapse did not appear to be associated with age or gender. Although not statistically significant, there was a trend for patients with a chondroblastic subtype of osteosarcoma, or a location in the tibia or fibula, to have a higher risk for late relapse.