Recent data indicate that stem cells exist in many tissues, including skeletal muscle, liver, and the central nervous system, some of them not known classically as having stem cells. The unexpected plasticity and the tremendous disease implications of these findings have created a lot of excitement (1, 2). However, a major obstacle in these areas has been a lack of molecular markers and of the precise in vivo localization of the putative stem cells. Because epidermis is an excellent example of a selfrenewing tissue containing stem cells, it is of interest to examine the current status of this field. Like stem cells of other tissues, epidermal stem cells are important because they not only play a central role in homeostasis and wound repair, but also represent a major target of tumor initiation and gene therapy.

Perhaps the most universally accepted criteria for keratinocyte stem cells are that they are normally slow-cycling (or, perhaps more accurately, rarely cycling) in vivo; that they can self-renew and are responsible for the long-term maintenance of the tissue; that they can be activated by wounding or by in vitro culture conditions to proliferate and to regenerate the tissue; and that they have a high proliferative potential (3–6). The slow-cycling attribute is particularly important biologically because it conserves the cell’s proliferative potential and minimizes DNA replication-related errors. The rare divisions of stem cells give rise to, on average, one stem cell and one transit amplifying (TA) cell, which has a limited proliferative potential. On the exhaustion of their proliferative potential, the rapidly proliferating TA cells undergo terminal differentiation. The slow-cycling stem cells can be identified experimentally as the ‘‘label-retaining cells’’(LRCs)(7). This is done by long-term labeling of all of the cells with a DNA precursor such as [3H] thymidine or bromodeoxyuridine (BrdUrd), followed by a chase period that results in the dilution of the label from all of the rapidly cycling TA cells, but not from the slow-cycling stem cells (7, 8). Using this approach, two groups recently discovered that the label-retaining, presumptive keratinocyte stem cells of hairy