It is known that cancer is caused by an accumulation of mutations in DNA. Many genes have been associated with tumour progression either through germline or somatic mutations, but mutations in these genes by no means account for all instances of the disease. The availability of the completed human genome sequence and reduced costs of sequencing have allowed large-scale screens to uncover genes that are somatically mutated in cancer. In this issue, Chanock and colleagues present a screen of 91 breast cancers for somatic variants in a set of 21 genes.