In contrast to other cancers for which screening is advocated (ie, breast, cervix, and colon cancer), the optimal treatment of LC entails the partial removal of a vital organ. Furthermore, the risk of LC is higher among smokers with advanced COPD (which correlates with all-cause mortality rate, particularly with coronary heart disease16–). Consider the following hypothetical scenario. Six thousand prescreened male smokers with widely varying coronary risk factors and pulmonary function levels, and mean values of 60 years of age, height of 69 inches, and FEV1 of 2.2 L (70% of the predicted value [3.1 L]) are randomly divided into two groups of 3,000 individuals each. One group (IG) is radiographically screened, and the other (CG) is not. LC develops in 10% of individuals, equally distributed between the IG and the CG, all in the first year of screening. In 200 individuals, the LC is aggressive; in 200, it is nonaggressive; and in 200, it is overdiagnosed. Assume further that all resectable LCs occur in the left upper lobe and are treated by lobectomy, that excess deaths from respiratory failure, pneumonia, or coronary disease occur when the mean FEV1 falls to 1 L, that the rate of FEV1 decline (55 mL/yr17) is unchanged by surgery, and that the risk of pneumonia is increased by the surgically induced anatomic distortion and pleural reaction. With these assumptions, surgery would reduce the mean life expectancy from 22 to < 11 years (ie, the mortality rate would be doubled (see Appendix A). Survival and mortality would be nearly equal in the IG and CG among persons with aggressive LC. Survival would be markedly increased (due to lead-time bias), and the mortality rate would be decreased slightly in the IG compared to the CG among persons with nonaggressive LC. However, in subjects with overdiagnosed LC, the survival would increase in the IG, but the mortality rate would be double that in the CG. The net effect would be an increased incidence, survival, and mortality rate in the IG compared with the CG, mirroring the MLP and Czech experience.