Central nervous system (CNS) tumours are the major cause of cancer-related deaths in people under 40. Comprehending their variety in terms of genetics, epigenetics, cell of origin and phenotypic properties, as well as interactions with the microenvironment and whole-organism physiology, is critical for developing much needed personalized therapies. We are interested in neural proliferation and how its disruption can lead to immortal and invasive tumours. We start from understanding obtained with the fruitfly Drosophila melanogaster and then investigate evolutionary conservation in mammals of the molecular and cellular processes found. The power of Drosophila genetics has promoted numerous conceptual and mechanistic insights concerning neurogenesis, and has led to identification of mutations leading to tumour formation, many of which are conserved in humans. Approximately one third of human genes encode proteins of uncharacterised function so there remains great need for gene function discovery, in addition to ascribing physiologically significant roles to known genes. The genome of Drosophila frequently contains a single orthologue per few mammalian homologues yet includes over 70% of counterparts for known human disease genes.