Epithelial cells are continuously sloughed into the environment and replaced by similar cells from underneath. This coordinated homeostasis is maintained by a subpopulation of keratinocyte stem cells with high proliferative potential, located at the basal layer of the epidermis and thought to remain in the tissue for life. Identifying and isolating epidermal stem cells has proven difficult, and the lack of a widely accepted method has hampered their potential for use in tissue engineering, wound repair, gene therapy, and as cell therapy agents. In the October 15 Journal of Cell Science, Hong Wan and colleagues at the Guy's, King's and St. Thomas' School of Medicine report a novel strategy for the isolation of epidermal stem cells that combines a previously proposed marker with selection for low levels of expression of a surface protein (Journal of Cell Science, 116:4239-4248, October 15, 2003).