The race to determine the genetic steps in the progression of lung cancer has recently intensified, in large part because of the launch of new translational multidisciplinary initiatives by the U.S. National Cancer Institute known as SPORE (Specialized Projects of Oncology Research Excellence) grants. Thus, the molecular genetics of an often-ignored major killer, lung cancer, are now being unraveled by several groups. In this issue of the Journal, a pioneering group in lung cancer genetics (7) describes loss of chromosome 9p in preneoplastic lesions in patients with non—small-cell lung cancer. Initially described as a rare event in preliminary allelotypes (2), chromosome 9p loss now represents the most common genetic change in non-small-cell lung cancer and in many other types of human neoplasms. Deletions of chromosome 9p21 originally identified a puta- tive tumor suppressor gene locus in leukemia (3). Moreover, genetic linkage studies demonstrated that the familial melanoma locus also resided on chromosome 9p21 (4). Subsequent studies in primary tumors and cell lines began to reveal the presence of deletions, including homozygous deletions at chromosome 9p21 in various tumor types such as those of the lung (5-7), head and neck (8), bladder (9), and many others. These studies began to demonstrate that 9p loss was among the most common genetic events yet described in human cancer.