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Cancer is a major contributing cause of morbidity and mortality in the Eastern Mediterranean region. The aim of the current study was to estimate the cancer burden attributable to major lifestyle and environmental risk factors. We used age‐, sex‐ and site‐specific incidence estimates for 2012 from IARC's GLOBOCAN, and assessed the following risk factors: smoking, alcohol, high body mass index, insufficient physical activity, diet, suboptimal breastfeeding, infections and air pollution. The prevalence of exposure to these risk factors came from different sources including peer‐reviewed international literature, the World Health Organization, noncommunicable disease Risk Factor Collaboration, and the Food and Agriculture Organization. Sex‐specific population‐attributable fraction was estimated in the 22 countries of the Eastern Mediterranean region based on the prevalence of the selected risk factors and the relative risks obtained from meta‐analyses. We estimated that approximately 33% (or 165,000 cases) of all new cancer cases in adults aged 30 years and older in 2012 were attributable to all selected risk factors combined. Infections and smoking accounted for more than half of the total attributable cases among men, while insufficient physical activity and exposure to infections accounted for more than two‐thirds of the total attributable cases among women. A reduction in exposure to major lifestyle and environmental risk factors could prevent a substantial number of cancer cases in the Eastern Mediterranean. Population‐based programs preventing infections and smoking (particularly among men) and promoting physical activity (particularly among women) in the population are needed to effectively decrease the regional cancer burden. What's new? How many cancers could be prevented by lifestyle changes? These authors set out to quantify the fraction of the cancer burden attributable to 8 major lifestyle factors in the Eastern Mediterranean region, which includes 22 countries. The risk factors they analyzed included smoking, alcohol, infections, and high BMI. Fully one third of new cancer cases among adults, they found, could be prevented by reducing exposure to risk factors. They conclude that public health programs to promote physical activity, reduce smoking, and prevent infections, would significantly reduce cancer mortality in this region. [ABSTRACT FROM AUTHOR]