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Objective: To assess the association of proportions of fatty acids in cholesterol esters with the risk of premature death from cancer in middle aged men., Design: Prospective cohort study., Setting: Paris, France., Subjects: 3277 working men aged 36-52 in 1981-5., Main Outcome Measures: Cancer mortality during an average of 9.3 years of follow up., Results: 59 men died of cancer during follow up. The age adjusted relative risks for men in the highest thirds of the distribution of the proportions of linoleic, palmitoleic, and oleic acid in cholesterol esters as compared with those in the corresponding lowest thirds were 0.16 (95% confidence interval 0.05 to 0.51), 3.39 (1.63 to 7.05), and 4.22 (1.95 to 9.12), respectively. Adjustment for and stratification by smoking, alcohol consumption, serum cholesterol concentration, and body mass index did not alter the results. At the time of examination subjects with cancer had a lower intake of polyunsaturated fats, assessed by 24 hour recall, than those without cancer (13.2 v 17.4 g/day, P < 0.01)., Conclusions: Monounsaturated and polyunsaturated fatty acids of cholesterol esters are strong biological markers that predict premature death from cancer in French men. Consistently, intake of polyunsaturated fats did not seem to increase the risk of death from cancer. The association of biological markers of dietary fat intake with incidence of and mortality from cancer should be investigated prospectively in other populations.