HOX homeodomain proteins are thought to be master developmental regulators of tissue patterning during embryogenesis. These DNA binding proteins also have diverse roles in adult cell function, and derangement ofHOXgenes has been associated with several types of cancer. In this chapter we present protocols for the immunohistochemical localization of HOX proteins in the epidermis. We also providein situhybridization protocols for detection ofHOXgene mRNA transcripts in the epidermis.