This unit provides two models of oral carcinogenesis (hamster cheek pouch and rat tongue), as well as more simple procedures to induce squamous cell carcinomas (SCCs) in mouse skin. The most significant usage of these models has been their application in studying the molecular pathology of the genesis and multi-step progression of tobacco-associated SCC. Nevertheless, these protocols have been used frequently as in vivo bioassays to demonstrate the chemopreventive and, to a lesser extent, the chemotherapeutic effects of numerous compounds. Several examples, using four different carcinogenesis protocols, are presented with detailed steps on how to elicit squamous lesions and when and how to apply test compounds that could have either cancer chemopreventive or chemotherapeutic effects.