Mouse skin has been used extensively as a model system to study the development of cancer. Recent emphasis has been focused on elucidating the molecular mechanisms by which chemical carcinogens or tumor promoters cause the growth of cutaneous malignancies. In this regard, many transgenic or knockout mouse models have been generated in order to have a particular gene of interest overexpressed or knocked out in the epidermis of the skin. We have used a proteomics approach of protein separation using 2D gel electrophoresis and protein identification using mass spectrometry to study the molecular profiles of the epidermis in several transgenic mouse skin models. Identification of altered expression of proteins can shed light on the molecular processes that have been perturbed in these mouse models.