Cure rates for many paediatric cancers have improved dramatically in the last 20 years largely due to the coordinated efforts of both oncologists and scientists in facilitating globally collaborative research and clinical trials under the auspices of the Children’s Oncology Group (COG) in the USA and European cancer networks. This effort has contributed to both improved cure rates and a reduction in the incidence of treatment side effects due to the focused targeting of treatment intensification to specific tumour molecular sub-types. In this talk I will present an overview of the current state of knowledge in paediatric cancer molecular pathology, and the role my laboratory plays in both paediatric cancer biomarker detection and in the identification of paediatric patients at risk of malignancy.