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 to possess malignant phenotypes. Several genetic and epigenetic changes are common to all lung cancer histologic types, while others appear to be cell type specific. However, specific roles of the genes undergoing mutations and the order of cumulative molecular changes that lead to the development of each lung tumor histologic type remain to be fully elucidated. Recent findings of molecular abnormalities in normal appearing and preneoplastic bronchial epithelium from patients with lung cancer and chronic smokers suggest that genetic changes may serve as biomarkers for early diagnosis, risk assessment and monitoring response to chemoprevention.