Little is known about how the genotypic and molecular abnormalities associated with epithelial cancers actually contribute to the histological phenotypes observed in tumours in vivo. 3D epithelial culture systems are a valuable tool for modelling cancer genes and pathways in a structurally appropriate context. Here, we review the important features of epithelial structures grown in 3D basement membrane cultures, and how such models have been used to investigate the mechanisms associated with tumour initiation and progression.