In a population-based sample of women diagnosed with first primary breast cancer, we aimed to understand whether the association between prediagnostic recreational physical activity (RPA) and all-cause or breast cancer-specific mortality was modified by gene promoter methylation (which regulates gene expression) in a panel of 13 breast cancer-related genes (APC, BRCA1, CCND2, CDH1, DAPK1, ESR1, GSTP1, HIN1, CDKN2A, PGR, RARβ, RASSF1A, and TWIST1) measured in tumor tissue. The gene discussed is ESR1; the disease is breast cancer.