The studies reviewed here investigate the association between folate status and DNA methylation in cancer tissues. We evaluated tissue vitamin levels and global DNA methylation, a biomarker of neoplasia, in normal lung and lung cancer tissues. Lung squamous cell carcinoma tissues exhibited global DNA hypomethylation, with decreased folate and vitamin B-12 concentrations, and increased vitamin C concentrations, relative to matched uninvolved control tissues. Breast cancer tissues also had globally hypomethylated DNA and decreased vitamin B-12 and vitamin C levels, but folate concentrations were elevated in breast cancer tissues. Global DNA methylation status in buccal mucosal cells may reflect global methylation status in lung tissues, because there was a significant association between global DNA methylation in buccal mucosal cells and malignant tissues of the lung, but not between methylation in peripheral leukocytes and lung tissues. We found that global DNA hypomethylation, as assessed by a radiolabeled 5-methylcytosine technique, was associated with susceptibility for development of lung cancer, which is involved in the progression of the disease. DNA methylation was also associated with the development of squamous cell carcinomas in whites but not in blacks. Overall, these studies suggest that global DNA methylation patterns may vary depending on the type of cancer, that tissue vitamin levels are associated with global DNA methylation status and that ethnicity should be considered in studies of DNA methylation.