Since it was first suggested that high dietary fat is a risk factor in colon cancer, there have been several studies to test this hypothesis. Epidemiologic studies suggested a positive association between dietary fat and colon cancer. Laboratory animal model studies demonstrated that not only the amount of fat, but also types of fat differing in fatty acid composition are important determining factors in colon tumor development. Chemically-induced colon tumor incidence was increased in rats fed the semipurified diets containing 23% corn oil, safflower oil, lard or beef tallow (high-fat) as compared to those fed 5% corn oil, safflower oil, lard or beef tallow diets (low-fat). Diets containing 23% coconut oil, olive oil or fish oil, or high-fat diets containing varying levels of trans fat, had no colon tumor-enhancing effect compared to their respective low fat diets. The stage at which the effect of dietary fat is exerted appears to be mostly during the post-initiation phase of colon carcinogenesis. Lack of a colon tumor enhancing effect of dietary fish oil is observed both during the initiation and postinitiation phases. The mechanisms by which various dietary fats increase colon carcinogenesis are not fully understood. In most instances, however, the high-fat diet appears to enhance tumorigenesis through elevation of agents, such as secondary bile acids, that act as promoters of tumor development. Lack of colon tumor promotion by dietary fish oil and trans fat appears to be mediated through their effect on mucosal ornithine decarboxylase activity, colonic secondary bile acids and/or prostaglandin synthesis.