The cell of origin of prostate cancer is still unknown. The identification of these cells depends on understanding prostate cell differentiation lineage during development as well as adult prostate epithelium renewal. Recent advances in the field have shed light on the hierarchical relationship between epithelial prostate cells. On the basis of this knowledge, the isolation and characterization of prostate cancer stem cells may now be possible and could provide an explanation for the known clinical and molecular heterogeneity of human prostate cancer.