In this chapter, recent literature on human and mouse normal mammary gland and breast cancer stem/progenitor cells will be reviewed. Part of these data will be gathered from studies performed on stem/progenitor cells in vitro expanded as multicellular spheroids, called mammospheres (MS). It will be highlighted that the available data support the notion that normal and putative cancer stem cell gene expression patterns are close to the basal-like phenotype. Such a phenotype identifies the normal mammary gland cell compartment that is supposed to harbor stem/progenitor cells as well as a subset of highly aggressive/metastatic breast carcinomas lacking estrogen receptor alpha (ERα) expression and overexpressing cytokeratin 5/6 (CK5/6), epidermal growth factor receptor (EGFr), interleukin-6 (IL-6), Notch-3, Jagged-1, carbonic anhydrase isoenzyme-IX (CA-IX), vimentin, and SNAI gene family members. It will be then argued that understanding the regulation of basal-like gene expression profile is expected to provide an insight on normal and cancer stem cell–controlling mechanisms. In particular, it will be pointed out that the pro-inflammatory cytokine IL-6, the stem cell regulatory gene Notch-3, its ligand Jagged-1, and the hypoxia survival gene CA-IX share a molecular machinery that promotes invasive behavior and survival of normal mammary gland and breast cancer stem cells. It will be also reported that, in normal mammary gland and breast cancer cells, the SNAI gene family members govern the onset of an undifferentiated mesenchymal phenotype that parallels the gain of a basal-like/stem cell–like phenotype.