As all epithelial cells are exposed to similar environmental conditions, it seems likely that many cells undergo mutagenesis simultaneously. Clinically, this is frequently apparent, as 10-20% of patients with lung cancer have another epithelial cancer arise, either concurrently, or at some later time in their course. The predisposition for development of second malignancies also affects other epithelial surfaces, for example, there is a strong tendency for patients with cancer of the head and neck to develop a second malignancy (bronchogenic lung cancer) in the aerodigestive tract. Despite decreases in the smoking rate overall in the United States, projections through 2025 indicate that there will still be 100,000 deaths annually from lung cancer and other smoking-associated cancers. Therefore, it would be of great benefit to patients at risk of developing lung cancer to identify these changes prior to the development of invasive malignant lesions. This is particularly true of patients who have already developed a cancer, or in patients with a strong family history who may have occupational (eg., asbestos) or habitual (eg., cigarette smoke) exposure to carcinogens. Identification of cancers in the pre-clinical stage has been attempted previously, for example with screening chest x-rays or sputum cytologies, however, these approaches have not proven to be beneficial, as current detection methods are not sensitive enough to identify early, non-phenotypic changes. The proposal outlined herein is designed to clarify this issue by examining bronchial tissue from patients at risk for development of a second cancer (patients undergoing primary resection for cure of bronchogenic lung cancer) and assessing the biopsy tissue for the presence of chromosomal abnormalities and mutations in the h- and k-ras protooncogenes. These changes may be present for long periods of time in airway epithelial cells prior to the development of overt pathologic changes, and methods to recognize these changes would be useful to assess and follow patients at risk for developing malignancy.