Our understanding of the molecular pathology of lung cancer is advancing rapidly with several specific genes and chromosomal regions being identified. Lung cancer appears to require many mutations in both dominant and recessive oncogenes before they become invasive. Several genetic and epigenetic changes are common to all lung cancer histologic types, while others appear to be tumor-type specific. The identification of those specific genes undergoing such mutations and the sequence of cumulative changes that lead the neoplastic changes for each lung tumor histologic type remain to be fully elucidated. Recent findings in normal and preneoplastic bronchial epithelium from lung cancer patients and smoker subjects suggest that genetic changes may provide in this neoplasm new methods for early diagnosis, risk assessment, and for monitoring response to chemoprevention.