The epidermis is the stratified epithelium that covers and protects the body from external damage. This tissue undergoes continuous cell renewal throughout the life of the individual at the expense of a pool of pluripotent cells, some of them lie in a well defined niche in the hair follicle known as the bulge. Epidermal tumours are the most frequent type of cancer in human populations, as a consequence, the development and progression of these tumours have been extensively characterised and a number of mouse models generated. Over the last years several findings suggest that a subset of cells, named cancer stem cells, could play an important role in tumour development; however, the identity of these cells remains unknown in most cases. Understanding the biology of these cells and their implication in tumour development and progression is crucial to design therapies aimed to target cancer stem cells. In this scenario, the epidermis emerges as a good model to gain deeper insight into the role of adult stem cells in carcinogenesis. Here we summarise recent findings in the field using genetically manipulated mice and how these can be translated to humans.