Several aspects of Western diets, alcohol use, and exercise patterns which are related to the risk of colorectal cancer have systemic effects in common. Those which increase the risk of colorectal cancer are positively associated with serum triglycerides and plasma glucose; those which decrease risk are negatively associated with serum triglycerides and plasma glucose. These observations suggest the hypothesis that serum triglycerides and/or plasma glucose may themselves be associated with colorectal cancer risk. Evidence for associations between colorectal neoplasia and triglycerides and glucose comes from two recent studies of adenomatous polyps, presumed precursors for colorectal cancer, and from previous studies of diabetes and cancer. In addition, three randomized trials, one in humans and two in animal models, suggest that diets which would be expected to increase serum triglycerides and plasma glucose increase the levels of cellular indicators of colorectal cancer risk. Biological mechanisms explaining associations between colorectal neoplasia and serum triglycerides and/or plasma glucose might involve luminal or circulatory effects: (a) triglycerides and/or glucose may be associated with fecal bile acids, acids which are positively associated with colorectal cancer risk ire epidemiological studies and which promote colorectal cancer in animal models; (b) serum triglycerides and/or plasma glucose might influence circulating hormones, such as insulin, which might themselves be involved in cancer development; (c) serum triglycerides and/or plasma glucose might be indicators of energy available through the circulation for neoplastic cells. Future research should examine the associations between the risk of colorectal neoplasia and serum triglycerides and plasma glucose, explore possible biological mechanisms, and develop an understanding of whether biological processes involving triglycerides, glucose, and insulin may be common to a number of sites of cancer.