Triple-negative breast cancers (TNBCs) are a diverse set of aggressive breast cancers that lack expression of estrogen and progesterone receptors, and lack HER2 amplification. Gene expression profiling has revealed distinct subsets of TNBCs, each characterized by unique patterns of gene expression and genomic changes. Comparative analysis of gene expression profiles also suggests that the different subclasses of TNBCs may arise from specific sets of mammary progenitor cell populations. In this article, recent data regarding characterization of a human mammary stem cell hierarchy and its relationship to the pathogenesis of subsets of triple-negative breast cancers will be reviewed.