Cancer is the leading social and healthcare problem of the twenty-first century. The aim of primary prevention is to decrease the incidence of cancer by avoiding the known causes and risk factors. Nevertheless, it has been estimated that cancer diagnoses could be halved through primary prevention measures. A comprehensive review of the scientific evidence regarding the main carcinogens and risk factors and primary prevention recommendations have been put forth based on this evidence. The GRADE scale has been used to classify the grade of evidence. We present the scientific evidence and recommendations for primary prevention of the major modifiable risk factors: smoking, alcohol, diet, obesity, physical activity, occupational and environmental factors, ultraviolet radiation, infections, and socioeconomic factors. Primary prevention is a simple, effective means to lower the incidence of cancer. Preventive measures must be circulated in the fight against cancer.