Carrot-Zhang et al. studied the effects of ancestry on mutation rates, DNA methylation, and mRNA and miRNA expression. Using 10,678 patients across 33 cancer types from The Cancer Genome Atlas, they determined that ancestry effects occur in a tissue-specific manner. They also identified that FBXW7, VHL, and PBRM1 cancer mutation rates differ by ancestry. This work reveals the importance of accounting for ancestry as a potential confounder in understanding cancer and potential treatments.