MDM2 gene amplification has been reported in more than 60% of low-grade osteosarcomas of the jaw compared to 12% in conventional osteosarcomas (Fig. 2b) [19, 20], whereas immunohistochemistry against MDM2 (and CDK4) is considered sensitive but not specific, and only MDM2 amplification detected by FISH strongly argues in favour of osteosarcoma and can be helpful to distinguish low-grade osteosarcoma from its fibro-osseous mimics. Here, CDK4 is linked to osteosarcoma.