Classical epidemiologic studies have made important contributions to identifying the etiology of most common cancers and have had substantive public health impact. Molecular epidemiology is an extension of classical epidemiologic research to incorporate biochemical and molecular biomarkers with questionnaire data to advance our understanding of mechanisms of carcinogenesis and of events between exposure and cancer development. Risk prediction, prognostication, and therapy prediction are the clinical uses of molecular epidemiology in cancer management. Lifestyle and environmental factors associated with carcinogenesis also strongly affect epigenetic statuses, and thus epigenetic mechanisms may mediate environmental influences on gene expression and even diseases, resulting in a focus of epidemiologic investigation. DNA methylation can be studied on candidate genes or on a genome-wide scale, although the genotype is fixed at conception but the epigenome is dynamic. Unlike simple genotyping, the levels and patterns of epigenetic changes differ in different tissues and cell types, and may not reflect events in target tissues. Still as a possible risk factor and surrogate marker for liability to cancer, the methylation statuses of blood leukocyte DNA seem to be ideal for the analysis and are emerging as a new scope. Epigenetic changes in comparison with genetic ones are reversible and are acquired in a gradual manner. These epigenetic features offer a huge potential for prevention strategies. Copyright © 2010 Elsevier Inc. All rights reserved.