In this article, we have described and compared the advantages and disadvantages of two potential animal cancer models (the hamster buccal pouch cancer model and the VX2-induced rabbit cancer model) for human squamous cell carcinomas of the oral mucosa. Currently, no animal cancer model is perfectly applicable to human oral squamous cell carcinomas. This is because the hamster buccal pouch cancer model has a different etiology and genetic constitution compared with human oral carcinomas. In addition, the VX2-induced rabbit cancer model is not produced in situ and, consequently, its natural behavior is totally reliant on the location of transplantation. Nonetheless, with the use of these two animal cancer models together, researchers could evaluate different aspects of the cellular and molecular biological characteristics or assess potential novel treatment regimens for squamous cell carcinomas of the human oral mucosa.