In this study, we globally analyzed genomic DNA methylation, correlated with gene expression profiling, and identified GNB4 that was silenced by DNMT3B-mediated DNA methylation in both fulvestrant-resistant (MCF-7/182R-6) and tamoxifen-resistant (MCF-7/TAMR-1) breast cancer cell lines. This evidence concerns the gene GNB4 and breast cancer.