It is now well accepted that colon cancer evolves from a multi-step process and is a disease strongly influenced by environmental factors, with diet being one of the most important modifying agents. Among dietary factors, there is cogent evidence indicating a protective effect of fish oil feeding with respect to colonic tumor development. We have recently demonstrated that the balance between colonic epithelial cell proliferation and programmed cell death (apoptosis) can be favorably modulated by feeding fish oil, containing n-3 polyunsaturated fatty acids, specifically, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We propose that the suppression of colonic tumor development by dietary n-3 polyunsaturated fatty acids may be due to an effect on the subcellular localization of oncogenic p21 ras. The potential for fish oil feeding to antagonize ras-dependent signal transduction is significant because the acquisition of chronically activated ras via mutation or overexpression is a relatively early step in colorectal cancer development.