The search for epidermal stem cells has gained the momentum as they possess unique biological characteristics and a potential in regeneration therapies. Several transcription factors and miRNAs have been identified as epidermal stem cell markers. However, the separation of epidermal stem cells from their progeny remains challenging. The introduction of single-cell transcriptomics pointed to the high degree of heterogeneity in epidermal stem cells imbedded within subpopulations of keratinocytes. Pseudotime inference, RNA velocity, and cellular entropy further enhanced our knowledge of stem cells, allowing for the discovery of the epidermal stem cell plasticity. We explore the main findings that lead to the discovery of the plastic trait within the epidermal stem cells and the implications of cell plasticity in regenerative medicine.