Abstract: ntroduction: Genetic intra-tumour heterogeneity (ITH) arises inevitably from the continual action of mutational processes. Selective pressure drives the expansion of individual cells, often leading to subclones that are detectable from bulk DNA sequencing. The occurrence of heterogeneity is of clinical importance, since different subclones have different proliferative potentials and responses to treatment. Here we present the first large-scale analysis of ITH using whole genome sequencing (WGS). Analysis of 2,800 tumours has yielded insights into the extent of heterogeneity in different tumour types, the order of acquisition of genetic aberrations, the evolution of mutational signatures, real-time estimates of landmark events in tumour development and the genetic drivers of subclonal expansion. Materials and Methods: The International Cancer Genome Consortium (ICGC) has obtained WGS of several thousand cancers, representing \textasciitilde 30 tumour types. The Pan Cancer Analysis of Whole Genomes (PCAWG) project has performed alignment and variant calling on 2,800 of these whole genomes and the PCAWG Working Group on Evolution and Heterogeneity, an international partnership of \textasciitilde 20 research groups, have carried out comprehensive analyses to identify the extent and nature of heterogeneity within the tumours and the mechanisms and processes that underlie tumour evolution. Results: Reconstruction of the subclonal architecture of over 2,000 tumours reveals variability in the extent of heterogeneity between tumour types. Separate analyses of different types of genetic aberration shows that some tumour types have more intra-tumour heterogeneity at the copy number level, while others acquire large numbers of single nucleotide variants subclonally. Chronological timing of whole genome duplications indicate that they commonly occur many years before diagnosis. Differences in mutational signatures of clonal and subclonal mutations indicate changes in the mutational processes operative on cancers at early and later stages of development. Within individual tumour types, some driver mutations are almost exclusively clonal, founding mutations, while others are very commonly subclonal. Subtypes may be defined from the agglomeration of numerous genomic features, indicative of the early determination of different pathways to cancer. Conclusion: Through a large-scale integrated analysis of whole genome profiles of over 2,000 cancers, we reveal differences in the evolutionary trajectories between tumour types and between individual tumours