Human stem cells have been isolated from embryos as well as diverse somatic tissues. Much efforts have been made to apply those stem cells for therapeutic purpose. Molecular dissection of "stemness" and differentiation process will provide us a clue to further understanding of stem cell biology. The fate of stem cell is determined in part by internal regulation mediated by transcriptional control. A set of genes related to specific functions might be expressed and suppressed upon external or internal signaling. Therefore, it is necessary to identify the complete gene expression profile that defines the stem cell. Moreover, we should verify the potential of therapeutic stem cells regarding differentiation, specific function, tumorigenecity, and toxicity rigorously before the clinical application. At present we have only limited information on "stemness" and differentiation into specific lineages. In the genome era, we can draw a molecular portrait on these functional and morphologic changes along the differentiation, trans-differentiation as well as de-differentiation using the DNA chip technology. We need to accumulate database for gene expression at various steps of stem cell differentiation, which will enhance our knowledge for research on and medical application of stem cell.