The potential applicability of specific carcinogen-derived biomarkers in chemoprevention trials against lung and oral cancer is discussed. At present, there are no examples of the use of these biomarkers in chemoprevention trials, but the principle has been established in chemoprevention trials directed at aflatoxin B1-induced liver cancer. Polycyclic aromatic hydrocarbons (PAHs) and tobacco-specific nitrosamines are among the most important carcinogens invoked as causes of lung and oral cancer. Biomarkers that are potentially practical for current application in chemoprevention trials are 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene-DNA adducts, as determined by HPLC with fluorescence detection, nitrosamino acids in urine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides in urine, nicotine metabolites in urine, and metabolites of cytochrome P450 substrates in urine. Biomarkers that need further development or exploration before application in trials include 7-methylguanine in DNA, tobacco-specific nitrosamine-DNA adducts, acrolein/crotonaldehyde-DNA adducts, PAH-protein adducts, acetaldehyde-protein adducts, pyrene metabolites in urine and benzo[a]pyrene metabolites in urine. Such carcinogen derived-biomarkers could be applied in chemoprevention trials to test the hypothesis that chemopreventive agents alter carcinogen metabolic activation and detoxification and, ultimately, risk for cancer.