Stem cell research has greatly contributed to the field of oncology with the identification and isolation of cancer stem cells from a variety of tumors. The discovery of rare subpopulations of cancer stem cells has indeed entirely changed the focus of cancer research. Normal adult stem cells and cancer stem cells can both self-renew and undergo a differentiation program that, in turn, gives rise to a high number of differentiated cells. Adult stem cells and their malignant counterparts share almost all of the same intrinsic and extrinsic factors to regulate self-renewal, differentiation and proliferation pathways. Fractions of normal and cancer stem cells are naturally more resistant to toxic injuries than any other cell type. Overall, these observations lead to the conclusion that adult stem or progenitor cells can eventually become malignant by generating cancer stem cells, which are responsible for the development and maintenance of the tumor mass. In addition, chemo-resistant cancer stem cells may cause the relapse of the disease following an apparent beneficial treatment. Indeed, the study of the biology of cancer stem cells might lead to the improvement of preventive cancer diagnosis and to the development of novel therapeutics, which must be designed to selectively target malignant stem cells without affecting normal adult stem cells.