The results of the present study suggest that a subset of human breast cancer cell lines express a hypermethylator phenotype that is characterized by concurrent methylation-dependent silencing of a number of genes, including a specific set of genes with excellent predictive power (CDH1, CEACAM6, CST6, ESR1, LCN2, and SCNN1A) that are involved in a wide range of neoplastic processes. This evidence concerns the gene ESR1 and breast cancer.