The epidermis is a model particularly well suited to the study of cell proliferation and differentiation, and of alterations of these processes such as carcinogenesis. Compartmentalization exists in this tissue, with the proliferative, less differentiated cells confined to the basal layer and the terminally differentiating, non-proliferative cells moving upwards to the surface through distinct layers. Different genes are expressed throughout this process in a stage-of-differentiationspecific manner, and their promoters have been very useful in directing precise gene expression in transgenic mice. Other attractive characteristics of the epidermis include its external localization, which facilitates manipulation and observation, the possibility of obtaining primary keratinocytes that can be easily cultured and manipulated in vitro, and the existence of well-established protocols for chemical and UV carcinogenesis. The latter are invaluable tools for assessing the in vivo functions of the genes targeted in transgenic mice. These characteristics have made the epidermis a widely used model system in recent years for the study of molecular mechanisms of carcinogenesis. A wealth of transgenic mice generated using epidermal-specific promoters, as well as knockout animals, have been used to examine the role of genes involved in processes such as cell cycle control, cell signaling, cell growth and differentiation, and angiogenesis in tumor and metastasis growth. Cre / loxP technology will allow a new generation of mice that allows the study of cancer genetics in a cell type-and time-controlled manner, more closely resembling the conditions found in the development of neoplasms.