Recent results have supported the cancer stem cells hypothesis in which tumors originate from tissue stem cells or their early progenitors and, as a result, produce tumors that retain stem cell properties. These properties include selfrenewal that drives tumorigenesis and differentiation that contributes to cellular heterogeneity. The number of these cells is very small, and is tightly controlled by the self-renewal pathway and the signals of their environment (niche). Evidence for the existence of cancer stem cells has been reported for a number of human cancers including leukemia, cancers of the breast, brain, and colon. Although our understanding of the biology of these cancer stem cells remains rudimentary, the existence of these cells has implications for current conceptualization of malignant transformation and targeted therapy for the treatment of cancer.