Abstract: We have characterised intra-tumour heterogeneity (ITH) across 2,778 whole genome sequences of tumours in the International Cancer Genome Consortium Pan-Cancer Analysis of Whole Genomes project, representing 36 distinct cancer types. We applied 6 copy number (CNA) callers and 11 subclonal reconstruction algorithms and developed approaches to integrate the results in robust, high-confidence CNA calls and subclonal architectures. The analysis reveals widespread ITH. We find at least one subclone in nearly all (96.7%) tumours with sufficient sequencing depth. Analysis using dN/dS ratios yields clear signs of positive selection in clonal and subclonal mutations and we find subclonal driver mutations in known driver genes. However, only 24% of subclones contain a driver mutation in a known driver gene, suggesting that a multitude of undiscovered late drivers exist and that tumours continue to undergo selection after tumourigenesis, at least until diagnosis. Consistent with other studies, we find that in 9% of tumours all clinically actionable mutations are subclonal, while 20% of tumours contain at least one subclonal actionable driver. These findings emphasise the relevance of ITH in treatment decision making. Distinct patterns of ITH emerge; for example, prostate, uterus and esophageal adenocarcinomas show high proportions of both subclonal single nucleotide variants (SNVs) and CNAs. Kidney chromophobe and pancreatic endocrine tumours also contain high proportions of subclonal SNVs, but few subclonal CNAs. On the other hand, hepatocellular carcinomas and head-and-neck and lung SCCs contain low proportions of subclonal SNVs and high proportions of subclonal CNAs. Mutational signature analysis reveals changes in signature activity. Exposures to UV light in melanomas and acid reflux in stomach and oesophageal cancers contribute more clonal mutations. While APOBEC and DNA damage repair response related signatures show increased activity in subclones. These findings highlight distinct evolutionary narratives between and within histologically distinct tumour types.