PURPOSE: We evaluated risk factors of cancer mortality based on a 40-year follow-up of the Corfu cohort (Seven Countries Study). MATERIAL AND METHODS: The population studied in this analysis consisted of 529 rural men (49 +/- 6 years old) enrolled in 1961. Since then, periodic visits every 5 years were made to define the causes of death of the participants. Cox proportional hazards models evaluated various risk factors in relation to cancer mortality. RESULTS: The death rate at the end of the follow-up was 87.1% (i.e., 461 deaths in 529 participants). Of those deaths, 118 (25.6%) were because of cancer (30 deaths were due to cancer of trachea, bronchus, and lung, and the rest were due to other malignant neoplasms). Cancer was the second cause of death in this cohort, after coronary heart disease. Age (hazard ratio, 1.05 per year; P < 0.05), smoking (hazard ratio, 1.97; P < 0.01), total serum cholesterol levels (hazard ratio, 0.95 per 10 mg/dL; P < 0.05), and body mass index (hazard ratio, 0.93 per 1 kg/m2; P < 0.05) showed a significant association with cancer deaths after controlling for physical activity status and anthropometric indices. It should be noted that the protective effect of total cholesterol on cancer mortality was observed only between 183 and 218 mg/dL baseline levels. CONCLUSION: Cancer was one of the leading causes of death in this cohort. Smoking was associated with increased risk of cancer, whereas moderate total serum cholesterol and increased body and mass index seemed to have a protective effect on 40-year cancer mortality.