Recently, substantial progress has been made in the identification and characterization of stem and progenitor cells in the mouse and human mammary gland. Furthermore, there is accumulating evidence that these cells might be targets for transformation during mammary carcinogenesis. On the basis of this stem cell concept, we propose a model in which the transformation of different subsets of stem and progenitor cells results in the diversity of breast cancer phenotypes, including expression of the estrogen receptor in breast cancers subtypes. This model has important implications for understanding mammary carcinogenesis. Furthermore, the concept of breast cancer as a disease of mammary stem and progenitor cells has profound implications for the development of new strategies for breast cancer prevention and therapy.