I have applied our high-throughput genomic/epigenomic technologies, such as high-density SNP arrays and next-generation sequencing (NGS) technology, to identifying genes that present as plausible candidates for contributing to breast cancer development. The genomic investigation has led to the identification of two putative oncogenes, IRX2 and TBL1XR1. Our research has provided direct experimental evidence supporting an oncogenic effect for TBL1XR1 and IRX2. Our epigenomic investigation has led to the identification of DNA methylation signatures that are selectively associated with clinical phenotypes such as lymph node involvement, histological grade, tumor size, and ER/PR/HER2 status. Our methylation signature recapitulates gene expression signature and can distinguish luminal versus non-luminal breast tumors. Furthermore, our methylation signature can provide information, beyond gene expression, to refine sub-classification of luminal breast tumors.