The concept of genetic susceptibility and interactions between genetic and environmental factors of risk is a new trend in molecular epidemiology studies of cancers. Micronuclei are biomarkers of chromosome damage due to genetic instability or exposure to environmental mutagens or carcinogens. The micronucleus assay in combination with fluorescent in situ hybridization discriminates between micronuclei containing acentric chromosome fragments (chromosome breakage) and micronuclei containing whole chromosomes (chromosome loss). A recent approach is to associate the biomarkers of genetic susceptibility, which take into account cancer susceptibility and interindividual differences in the response to a genotoxic exposure, and the micronucleus assay, which serves as a biomarker of interactions between the environment and the genetic material of the cell. Information is being gathered on how DNA damage and more particularly the frequency and centromeric content of micronuclei depend on the polymorphisms of genes implicated in xenobiotic metabolism (activation or detoxication), DNA lesion repair, or folate metabolism. For biomonitoring purposes, numerous confounding factors (age, sex, tobacco consumption) influence the micronucleus biomarker, and thus associating genetic polymorphisms to micronuclei would be useful to better define the prevention and prediction of cancer risk.