Recently, much excitement has been generated by strong suggestions that stem cells isolated from diverse somatic tissues may have a previously unsuspected degree of developmental or differentiation plasticity. For example, a hematopoietic stem cell may be capable of producing mature liver cells, muscle tissue or even neurons. Similarly, central nervous system stem cells or muscle stem cells may be capable of producing mature blood cell populations. These observations have called into question several fundamental dogmas of developmental biology. In addition, these observations offer extraordinary promise in the clinical setting. It is of paramount importance to rigorously assess the suggested plasticity phenomena using precise clonal analysis. In order to explore the plasticity phenomena in more direct ways, it is necessary to develop in vitro systems where such behavior can be recapitulated in a well-defined setting. Finally, stem cell plasticity will be governed, at least in part, by cell-autonomous mechanisms: that is, those mediated by the panel of gene products expressed in stem cells. Therefore, it is necessary to identify the complete gene expression profile that defines the stem cell.