In a human embryo it takes 8 weeks after fertilisation for the skeleton to begin to form, one of the last organs to develop before becoming a foetus. Mesenchymal progenitors, derived from neural crest cells, differentiate into chondrocytes where the skeleton is generated as a mostly cartilage template. Other mesenchymal progenitors envelop the template, activate runt related transcription factor 2 (RUNX2) and bone morphogenetic protein 2 (BMP2) and differentiate into osteoblasts, where an osteoid matrix is secreted and subsequently mineralised to become bone.1 During development and up to late adolescence, cellular proliferation enabling skeletal growth is restricted to the metaphysis and epiphyseal line or “growth plate”. It is in the growth plate of long bones where most bone cancers develop, hence the predominantly childhood incidence of the cancer. Primitive mesenchymal cells undergo transformation to form a heterogeneous group of bone malignancies. The most common type of bone cancer in children is osteosarcoma, mostly initiated by tumour protein p53 (TP53) mutations. The second most common type of bone cancer in children is Ewing sarcoma, mostly initiated by a EWS RNA binding protein 1-Fli-1 proto-oncogene, ETS transcription factor (EWSR1-FLI1) fusion. There are an average of 160 and 55 new cases of osteosarcoma and Ewing sarcoma, respectively, every year in the UK. Five-year survival for both cancer types is 50% when diagnosed early. Five-year survival is 15% when lung metastases are present at diagnosis. Treatment progress for bone cancer is poor when compared to other cancers such as breast where there is a twenty-year survival of 70%. Bone cancer requires extensive and sometimes disabling multimodal treatment. Chemotherapy for osteosarcoma includes methotrexate, cisplatin and doxorubicin, which were developed in the 1940’s and 1970’s. Chemotherapy for Ewing sarcoma includes vincristine, ifosfamide and etoposide, which were developed in the 1960’s and 1980’s. If the tumour responds well to chemotherapy and radiotherapy, wide area resection or amputation is performed. New understanding of bone cancer biology leading to better diagnosis and better treatments is required.