Abstract: Patients with epidermolysis bullosa were able to be cured through replacing the entire skin with stem cells. From incurable to curable disease, there is a long and winding road leading to the birth of skin stem cell therapy. It started from the technique unintentionally invented for culturing skin stem cells in vitro. Later on, scientists regenerated skin tissue in vivo using cultured stem cells, and successfully treated patients with deep burn on skin or chemical burn on cornea. At last, this technique was successfully used to cure skin genetic disease. This clinical breakthrough is a milestone for stem cell and gene therapies. Reviewing this journey, exhibiting the process of how these discoveries occurred, would provide a model and reference for gene and stem cell therapies in other fields.