Plasma homocysteine (Hcy), a well-known independent risk factor for coronary heart disease, is also a risk factor for cancer. Results froth our studies indicate that Hey could be used as a tumor marker. We found elevated circulating total homocysteine (tHcy) in cancer patients even though they were not treated with anti-folate drugs. In serial specimens froth cancer patients undergoing treatment, the change of tHcy coincided with the concentration of tumor markers. The rapid proliferation of tumor cells contributed to the much higher concentrations of circulating tHcy. Both concentrations of tHcy and tumor marker would increase in parallel during the growth of tumor cell, but only the Hey concentration would decline in response to tumor cell death. Several biochemical changes, including folate deficiency, oxidative stress, aberrant DNA methylation, and production of homocysteine thiolactone have been identified in association with hyperhomocysteinemia, which explained why elevated homocysteine eventually led to carcinogenesis. Conceivably, tHcy may be used as a more accurate tumor marker for monitoring cancer patients during treatment, and hyperhomocysteinemia as a risk factor for carcinogenesis. 2002 Elsevier Science B.V. All rights reserved.