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Smoking is an established risk factor for cancer. However, most studies have been carried out on western populations, and less is known about the impact in central and eastern Europe. Our objective was to investigate the association between cigarette smoking, educational level and risk of cancer in a Lithuanian population-based cohort study. The study included 6976 men initially free from cancer. During the follow-up (1978–2008), 1780 cancer cases were identified. Cox proportional hazards models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs). In addition, the burden of cancer attributable to smoking was assessed by the population attributable fraction. Following adjustment for age, education, alcohol consumption and BMI, for current compared with never smokers, highly significant and strongly elevated estimates were found for total (HR=1.79, 95% CI 1.59–2.02), tobacco-related (HR=2.52, 95% CI 2.16–2.95), upper aerodigestive tract (UADT) (HR=5.77, 95% CI 2.73–12.21), lung (HR=10.47, 95% CI 6.74–16.25), bladder (HR=3.31, 95% CI 1.71–6.41) and liver (HR=4.64, 95% CI 1.53–14.08) cancer. Findings suggest a lower risk of prostate cancer in current smokers. In addition, the occurrence of lung and UADT cancer was significantly elevated in men in the lowest educational attainment category. If smoking had not occurred, ∼23% of total cancer, 37% of tobacco-related, 77% of lung, 58% of UADT, 43% of liver and 45% of bladder cancer cases could have been prevented in this cohort of men. Cancer-control strategies focused on reducing smoking should be a public health priority.