An understanding of the molecular pathogenesis of lung cancer has evolved from classic cytogenetic studies and the use of restriction fragment length polymorphisms to encompass the definition of specific genetic abnormalities associated with this disease. Activation of the dominant class of oncogenes is frequent, with involvement of the ras and myc families of genes being the best defined. Several examples of inactivation at specific loci exist and have been related to the presence of tumor suppressor genes, most notably the retinoblastoma gene, p53, and a putative gene located on the short arm of chromosome 3. As our understanding of the nature and interactions between these numerous genetic events evolves, new opportunities for early diagnosis, prevention, and treatment will arise.