This perspective describes some commonly used animal models for the evaluation of potential chemopreventive agents in colon carcinogenesis. Special emphasis is given to the azoxymethane (AOM)/1,2-dimethylhydrazine (DMH) rat model and APCMIN mice, carrying a mutation in APC, a key gene in human carcinogenesis. In the AOM/DMH model, colon cancers are induced chemically by high dosages of carcinogen and tumours develop mainly in the colon through a multistep process similar to that observed in human carcinogenesis. In the APCMIN mice, carcinogenesis is spontaneous with no need of carcinogen administration but tumours develop mostly in the small intestine while colon tumours are less frequent. Moreover, the easy identification of preneoplastic lesions, such as aberrant crypt foci (ACF) and mucin depleted foci (MDF), in short-term studies make the AOM/DMH model a useful test for screening the potential chemopreventive efficacy of natural products.