The world’s largest and most comprehensive repository of somatic mutations found in cancer is celebrating its 20th birthday by adding 307,000 new genomic variants to its 24 million-strong database. With somatic mutations being the main drivers of tumor development, the Catalogue of Somatic Mutations in Cancer (COSMIC) is firmly established as a source of potential drug targets, for the discovery and validation of biomarkers associated with prognosis, treatment response and patient outcomes, and as a resource for characterizing the mutational landscape of individual tumors.