The 15% 5-year lung cancer survival the author cites in arguing against the existence of overdiagnosis and nonaggressive lung cancers applies to clinically diagnosed lung cancer; there is no plausible justification for ascribing equal lethality to the biological behavior of screen-diagnosed lung cancer. On the contrary, the Mayo study3reported a 5-year survival in the screened cohort of 35% vs 15% in the unscreened cohort, but the number of “advanced” lung cancers was identical in the two cohorts (and the screened cohort experienced a higher lung cancer mortality than the unscreened cohort). He contends that overdiagnosed lung cancer is an “ephemeral entity,” citing in support of this dictum the studies of Flehinger et al4and Sobue et al.5 The former is a Monte Carlo mathematical simulation of screening outcome employing four model parameters based on the Mayo Clinic data. It clearly did not address overdiagnosis, which is an empirical observation. Sobue et al5reported on 42 persons with screen-identified stage IA lung cancer who did not undergo surgery either because of refusal (65%) or medical contraindication (35%). Only 14% underwent either mediastinoscopy or CT (ie, they were most likely understaged). The majority had squamous carcinomas; only 12 patients (29%) had adenocarcinomas (peripheral adenocarcinomas, which have the most favorable prognosis, constituted 78% of the cases in the Early Lung Cancer Action Project [ELCAP] prevalence screen). Radiation therapy or chemotherapy, or a combination, was provided to 34 of the 42 persons. After 10 years of follow-up since diagnosis, all had died, 20% of causes other than lung cancer. Whether this outcome provides definitive evidence of the efficacy of nonsurgical therapy, or plausible evidence of overdiagnosis, I leave the reader to decide. The high prevalence of autopsy-detectable lung cancer in individuals who died of other causes, which McFarlane and his colleagues (cited in my initial article) provided in abundance, constitutes definitive evidence that lung cancer is not invariably the cause of death in individuals with this condition. Corroborative evidence for overdiagnosis bias is provided in my article and by Woloshin et al.6 In a recently published article originating in the Mayo Clinic, Swensen et al7 state, “The morbidity and mortality associated with radiation, biopsy and surgical procedures must be considered. Morbidity and mortality considerations are particularly disconcerting in cases of benign lesions and overdiagnosed cancers. Clinicians currently lack the ability to determine which cancers will be lethal and which ones are the result of overdiagnosis” [italics added]. The dictum that overdiagnosis bias does not exist entails its corollary: that a diagnosis of lung cancer confers immunity to death from all other causes. That screening results in overdiagnosis is indubitable; the issue is how often it occurs. Precise estimates would be contingent on the sensitivity of the screening method, the duration of follow-up of both cohorts, and the accuracy of tissue interpretation. Upper-limit estimates are constrained by the proportion of “missing cases” in the control group and, assuming equal cohort size, are given by the following formula: (No. of cancers in the screened group − No. of cancers in the control group)/(No. of cancers in the screened group). The figures are 22% in the Mayo Clinic study and 32% in the Czech study. Low-dose CT screening will necessarily increase overdiagnosis (and its adverse consequences) because earlier diagnosis will provide a greater duration of exposure to comorbidities. That the benefit of earlier diagnosis in individuals with nonaggressive lung cancer will offset this detrimental effect remains to be demonstrated.