In a case-control study probing the role of diet on the occurrence of colorectal cancer and undertaken in Athens, Greece, sera were collected from 100 cases and 100 controls, and serum total cholesterol, high-density-lipoprotein (HDL) cholesterol and triglycerides were determined. The biochemical results were analyzed in conjunction with nutrient intakes and a dietary score that summarizes in a linear way the dietary contrast between high-risk (high protein, saturated fat and dietary cholesterol; low vegetable) and low-risk (low protein, saturated fat and cholesterol; high vegetable) patterns. Cases with colorectal cancer had significantly (p less than 0.001) and substantially lower values of serum total cholesterol and particularly HDL cholesterol, but these associations did not reflect dietary practices, since protein intake and, to a lesser (and nonsignificant) extent, saturated fat and dietary cholesterol intake were higher among cases than among controls. In absolute terms, the dietary effect (as summarized in the linear dietary score) is more evident among persons with low serum total cholesterol and HDL cholesterol than among those with high levels of these serum lipids. These results indicate that a diet beneficial with respect to the risk of coronary heart disease is also likely to reduce the risk of colorectal cancer, even though low levels of serum total cholesterol and particularly HDL cholesterol represent important independent correlates of clinically overt colorectal cancer.