Higher intakes of folic acid-rich foods such as vegetables, legumes, and whole grains are associated with lower incidence of carcinomas in international comparisons and case-control studies. Deficiency of folic acid in experimental studies causes DNA damage that resembles the DNA damage seen in cancer cells. The requirement for folic acid in DNA synthesis and DNA methylation provides a plausible mechanism for a mutagenic effect of a low-folate diet. It is suggested that cancer can be initiated by DNA damage that results from folic acid deficiency. The relatively low level of folic acid in North American diets might be the underlying reason for high rates of many cancers in North America.