Chromosomal aberrations (CAs), micronuclei (MNi), and sister chromatid exchanges (SCEs) in peripheral lymphocytes have widely been used as biomarkers of genotoxic exposure and effects in humans. International collaborative studies have shown that a high level of CAs in lymphocytes is associated with an increased risk of overall cancer. The CA-cancer association is seen in subjects with known carcinogenic exposure but also in individuals with no known history of exposure to carcinogens. This suggests that a high CA level is an indicator of increased cancer risk regardless of the reason for the increase. Chromosome-type CAs appear to be more important than chromatid-type CAs in predicting cancer risk. As chromosomal fragments can form MNi, it is not surprising that an association has also been observed between lymphocyte MN level and overall cancer risk. It has not been possible to show an association between the frequency of SCEs in lymphocytes and cancer risk, possibly due to technical variation in SCE level and the fact that SCEs seem to represent homologous recombination repair of DNA. The reasons for the associations of CAs and MN with cancer risk are not clear, but undetected cancer does not explain them, because the time between the cytogenetic analysis and cancer diagnosis does not modify the risk. Carcinogenic exposure remains an explanation, as everybody is exposed through diet, general environment, and internal generation of genotoxic species. The results may also represent individual susceptibility to chromosomal damage. Cancer risk prediction by CA level has been observed in all studies published on the topic, despite the use of heterogeneous cytogenetic data, suggesting that the association is robust. There are suggestions that the association is stronger than hitherto assumed. If the accuracy of assessing the level of chromosome could be improved, individual cancer risk estimation might become possible.