Methionine metabolism and transmethylation are frequently altered in cancer cells. The alteration is often expressed as an inability of the cancer cells to grow when methionine is replaced by homocysteine in the culture medium, a condition that allows the growth of normal cells. This metabolic defect is termed methionine dependence. Methionine dependence may reflect an overall imbalance in transmethylation which results in the overmethylation of some substances and undermethylation of others within cancer cells. Many carcinogens affect various stages of methionine/transmethylation metabolism. The ultimate effect of the alteration of methionine/transmethylation metabolism may be the disruption of the regulation of genes involved in the oncogenic process. The known protective effect of methionine against cancer may be due to prevention of altered methionine/transmethylation metabolism or compensation of the altered metabolism.