The Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, comprising the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), has integrated and analyzed whole-genome sequencing data from 2,658 cancer genomes and their matched normal tissues across 38 tumor types. The consortium developed the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations, but in about 5% of cases, no drivers were identified. Chromothripsis, characterized by clustered structural variants, is a frequent early event in tumor evolution. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and exhibit multiple mechanisms to prevent telomere attrition. Germline variants affect patterns of somatic mutations, including point mutations, structural variants, and retrotransposition. The PCAWG Consortium has described non-coding mutations driving cancer, new mutational signatures, tumor evolution timelines, and the transcriptional consequences of somatic mutations. Cancer is the second leading cause of death worldwide, and its incidence is expected to increase significantly in the coming decades. The heterogeneity of cancer arises from Darwinian evolution, driven by stochastic mutations and selection. The PCAWG Consortium's work provides a comprehensive resource for understanding the genetic basis of cancer and advancing cancer research and treatment.The Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, comprising the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), has integrated and analyzed whole-genome sequencing data from 2,658 cancer genomes and their matched normal tissues across 38 tumor types. The consortium developed the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations, but in about 5% of cases, no drivers were identified. Chromothripsis, characterized by clustered structural variants, is a frequent early event in tumor evolution. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and exhibit multiple mechanisms to prevent telomere attrition. Germline variants affect patterns of somatic mutations, including point mutations, structural variants, and retrotransposition. The PCAWG Consortium has described non-coding mutations driving cancer, new mutational signatures, tumor evolution timelines, and the transcriptional consequences of somatic mutations. Cancer is the second leading cause of death worldwide, and its incidence is expected to increase significantly in the coming decades. The heterogeneity of cancer arises from Darwinian evolution, driven by stochastic mutations and selection. The PCAWG Consortium's work provides a comprehensive resource for understanding the genetic basis of cancer and advancing cancer research and treatment.