Abstract: Cancer is the ultimate disorder of the genome, characterised by not one or two substitutions, indels or copy number aberrations, but hundreds to thousands of acquired mutations that have been accrued through the development of a tumour. The set of mutations observed in a cancer genome is not simply a random accumulation of variants. It is the aggregate outcome of several biological mutational processes comprising an underlying mechanism of DNA damage mitigated by the DNA repair pathways that exist in human cells. Each mutational process will leave its distinctive mark or mutational signature on the cancer genome. Recently, we set out to extract the mutational signatures characterizing the mutational processes that have been operative in 21 whole-genome sequenced breast cancers. By integration of the mutational signatures identified in somatic substitution data with somatic copy number aberrations, we were able to construct the phylogenetic tree of a deep-sequenced (180X) cancer. I will describe how the digital nature of next-generation sequencing technology permits integrative and detailed analyses, such that the complexity and heterogeneity of breast cancers can be exposed.