Both mice and humans with increased Mdm2 levels, caused by a common single nucleotide polymorphism in the Mdm2 promoter (Mdm2SNP309), show a higher risk of developing sarcomas [14–16].Inactivation of p53 has been shown to accelerate tumour formation in genetically engineered mouse models, making it a primary focus of sarcoma research in the Rb pathway: The Rb signalling pathway is frequently altered in sarcomas, particularly osteosarcomas and rhabdomyosarcomas [17]. Here, MDM2 is linked to osteosarcoma.