Stem cells from different tissue origins share common characteristics, including selfrenewal capacity and tissue regeneration potential. Finding criteria to identify particular stem cell types, and understanding signaling pathways responsible for stemness, represent major research areas that will lead to a better characterization of the normal state of stem cells, thus improving our capability to use them for regenerative therapies. We will review here different approaches and experimental models liable to increase our knowledge of stem cells from human interfollicular epidermis. One of them, based on transcriptional profiling performed at the level of the global genome, consisted in searching universal molecular markers of stem cells. In other approaches, stem cells were studied at the level of specific characteristics. Understanding somatic stem cell properties such as quiescence or slow cycling state, and detoxification potential, led to the identification of phenotypes suitable for the selection of epidermal keratinocyte sub-populations with stem cell properties. The specific interests of these different research strategies will be discussed.