Environmental variables influence the incidence and expression of disease. Dietary fat is one environmental variable that has been associated experimentally and epidemiologically with alterations in certain types of tumorigenesis. Recently, detailed biochemical analyses have shown that not all fatty acid families possess the same tumor-promoting potential. In general, diets containing high levels of the n-6 polyunsaturated fatty acids have routinely enhanced tumorigenesis in lipid sensitive carcinogen-induced and tumor transplant tumor models, whereas diets with equivalent levels of n-3 polyunsaturated fatty acids have diminished tumorigenesis. At present, there is no definitive biochemical mechanism that fully explains these observations, but several possibilities have been proposed. One of the most attractive of these hypotheses is that each polyunsaturated fatty acid family has an individual effect on eicosanoid metabolism which determines its tumor-promoting potential. Regardless of current uncertainties about mechanisms of action, however, results of numerous animal models affirm the importance of qualitative, as well as quantitative, dietary lipid differences on tumorigenesis. This knowledge strengthens the probability that further advances in our understanding of lipid-tumor interrelationships will have important preventive and therapeutic medical benefits.