Epidermis contains similar to other tissue types a pool of cells responsible for self-renewal of the epithelium and its regeneration. These cells, so-called epidermal stem cells (ESC), are characterized by a high proliferative potential. Transit amplifying cells, as daughter cells of ESC, proliferate rapidly, but their potential is restricted. ESC are located in the bulge region of the outer root sheath of hair follicle or in the basal layer of interfollicular epidermis. In addition to keratinocytes, ESC also yield cells of sebaceous glands and of hairs. Stemness of ESC and initiation of differentiation are guided predominantly by Shh and Wnt signaling cascades. No specific markers of ESC were so far discovered but it is known that these cells highly express integrin receptors and keratin 15 and 19 are also present in these cells. Nuclear expression of p63 is also connected with ESC phenotype. Based on the emerging concept of of the sugar code study of endogenous lectins was initiated (Gabius et al., 2004). The growth regulatory endogenous lectin, galectin-1 and epitopes reactive for this lectin are expressed in nuclei of these cells. As indication for specificity, they are never bound by another endogenous lectin, galectin-3 (Purkrabkova et al., 2004). The establishment of squamous cell carcinoma appears to be connected with mutation of ESC or progenitor elements. Application of ESC in advanced cell therapy of skin defects and use the development of new treatment strategies of carcinomas arising from insights into mechanisms of differentiation in the treatment of carcinomas represent the perspectives for further research in this area.