Two genes are frequently mutated in OS, and both have predisposition syndromes leading to OS, namely Li-Fraumeni (TP53 mutation; 3–5% of OS have a germline mutation in TP53, while somatic mutations are seen in up to 95% of OS [9, 10]) and hereditary retinoblastoma (RB1 mutation; <1% of OS have a germline mutation in RB1 [11], while somatic mutations are seen in up to 64% of OS [11]). The gene discussed is RB1; the disease is hereditary retinoblastoma.