To understand relationships between breast tissue, ‘cells of origin’ and cancer stem cells in breast tumors, it is necessary to dissect the normal mammary epithelial hierarchy. We have isolated discrete populations of mouse and human mammary epithelial cells on the basis of cell surface markers and identified subsets that are highly enriched for mammary stem (MaSC), luminal progenitor and mature luminal cells. Recent studies have revealed that MaSCs are highly responsive to steroid hormones despite lacking expression of the estrogen and progesterone receptors. Transcriptome analyses of mouse and human mammary epithelial populations have led to the identification of multiple conserved genes/pathways and potential effectors of hormone action. In addition, the roles of a number of transcriptional regulators have been pinpointed along the mammary hierarchy using targeted mice. High throughput functional shRNA screens are currently being performed to identify novel genes governing stem cell proliferation and differentiation. To extend these studies, we have performed genome-wide studies to determine the epigenomes of primary mammary epithelial subtypes. Finally, the histone modification maps have been compared with the transcriptomes of these subpopulations, to gain insight into the molecular mechanisms that control cell-fate and differentiation programs in distinct epithelial subsets.