Childhood tumours are associated with congenital abnormalities suggesting that disruption of normal developmental processes may be linked with oncogenesis. Genetic and environmental exposures may combine to disrupt critical epigenetic processes during development, thus affecting gene-related signalling pathways and cellular function. This review examines the role of critical genes and processes regulating development such as the polycomb family and sonic hedgehog (SHH) as well as the Wnt signalling pathways and epigenetic variations (Snf5), methylation and loss of heterozygosity in controlling homeotic gene transcription and intracellular chromatin structure. The developmental and perinatal periods appears important as a window of opportunity for cancer research. Pediatr Blood Cancer 2009;52:755–760. © 2009 Wiley-Liss, Inc.