Our knowledge of the morphological heterogeneity of cancer has recently been augmented by the genomic heterogeneity revealed by the use of next-generation sequencing technology. We now know that no two cancers are alike and that even different regions within the same tumour vary in their composition. Tumours consist of multiple clonal populations and they evolve under Darwinian principles. This review summarizes some of the causes of such diversity and its implication for cancer management.