In this journal, in 2004,2I reviewed the studies supporting a genetic predisposition to lung cancer. Familial aggregation is a hallmark for inherited susceptibility, particularly when familial clustering of shared environmental factors, such as smoking, can be ruled out. The first reports of familial aggregation of lung cancer were published > 40 years ago.3Since then, a number of studies,4–6 with increasingly sophisticated designs and analytic approaches, have consistently demonstrated that individuals with a family history of lung cancer have an approximately twofold-increased risk of acquiring this disease, even after adjusting for family smoking patterns. A recent metaanalysis6 including 28 case-control studies revealed a 1.82-fold–increased risk (95% CI, 1.58 to 2.10) for lung cancer in individuals with a family history. In the 11 studies that evaluated risk among nonsmokers, risk associated with family history was still elevated (relative risk [RR], 1.51; 95% CI, 1.11 to 2.06). In addition, the four cohort studies included in the metaanalysis reported similar lung cancer risks in those with a family history (RR, 2.01; 95% CI, 1.62 to 2.50). It is well recognized that there are limitations to these studies, the most important of which are incomplete adjustment for smoking among relatives and lack of validation of family histories. However, even with these limitations, the consistency of findings across study designs and populations lends credence to these results.