Three major, fast developing lines of research are elucidating the biology of the mammary gland and its malignant transformation: phenotypical analyses of epithelial cells and mammary proliferative lesions, the identification, purification and characterization of mammary stem cells and breast cancer-initiating cells, and gene expression profiling studies using high-throughput microarray technologies. These three approaches are providing a flux of new, increasingly coherent information and are improving cellular and molecular models of breast epithelium and its malignancies. A new conceptual framework is emerging, altering viewpoints on the differentiation and transformation of the mammary epithelial cells. The combined effects of these progresses on our understanding of breast cancer biology should have major consequences on the way this disease is managed.