An extensive body of epidemiologic data has linked cigarette smoking to a wide variety of neoplastic diseases. Smokers have been found to incur an increased relative risk of mortality from cancer of the lung, head and neck, urinary tract, pancreas, and bladder. Recent work has also implicated smoking in the risk of leukemia and myeloma. The magnitude of these risks has prompted research aimed at identifying the carcinogens involved in specific smoking-related neoplasms, as well as potential genetic predispositions to the effects of these toxins. Mutations in tumor suppressor genes have been identified in both small-cell and non-small-cell lung cancer, and mutations in dominant oncogenes have been noted in the latter disease. A growing understanding of the molecular genetics of smoking-related cancers may translate into improved diagnosis and treatment. Detection of mutations in oncogenes or tumor suppressor genes in premalignant tissues might facilitate identification of individuals who have a hereditary predisposition to smoking-related carcinomas. In the future, tumor growth may be halted by replacement or substitution of mutated tumor suppressor gene functions or biochemical modulation of oncogene products. New forms of immunotherapy may also be targeted specifically toward mutant oncogenes in cancer cells.