Defects in apical-basal polarity regulation are associated with tissue overgrowth and tumorogenesis, yet the molecular mechanisms linking epithelial polarity regulators to hyperplasia or neoplasia remain elusive. In addition, exploration of the expression and function of the full complement of proteins required for the polarized architecture of epithelial cells in the context of cancer is awaited. This paper provides an overview of recent studies performed on Drosophila and vertebrates showing that apical polarity proteins of the Crumbs family act to repress tissue growth and epithelial to mesenchymal transition. Thus, these proteins emerge as potential tumor suppressors. Interestingly, analysis of the molecular function of Crumbs proteins reveals a function for these polarity regulators in junctional complexes stability and control of signaling pathways regulating proliferation and apoptosis. Thereby, these studies provide a molecular basis explaining how regulation of epithelial polarity is coupled to tumorogenesis.