Cancer, once thought to be caused largely by genetic alterations, is now considered to be a mixed genetic and epigenetic disease. The epigenetic landscape, which is dictated by covalent DNA and histone modifications, is profoundly altered in transformed cells. These abnormalities may arise from mutations in, or altered expression of, chromatin modifiers. Recent reports on the interplay between cellular signalling pathways and chromatin modifications add another layer of complexity to the already complex regulation of the epigenome. In this Review, we discuss these new studies and how the insights they provide can contribute to a better understanding of the molecular pathogenesis of neoplasia.