In the majority of primary osteosarcomas, the aetiology is unknown, but, for a minority, it occurs in the setting of a previous cancer, such as a hereditary mutation of retinoblastoma or an autosomic recessive mutation of p53 in the Li-Fraumeni syndrome (Huvos et al, 1977; Malkin et al, 1990; Alonso et al, 2001). The gene discussed is TP53; the disease is osteosarcoma.