The cost of mediastinoscopy did not materially influence the cost/benefit analysis. The cost ineffectiveness reflects the extremely low probability of identifying an AD. Reich et al2estimated that if 33,000 persons with presumptive S1S underwent mediastinoscopy, 32,982 persons would be confirmed with S1S (or, rarely, a disorder not requiring intervention) and that, at most, 8 persons with tuberculosis, 9 persons with Hodgkin disease, and 1 patient with non-Hodgkin lymphoma would be identified. Transbronchial lung biopsy for S1S, in the same analysis, was less efficient than mediastinoscopy because of its lower sensitivity. To our knowledge, no exceptions have been reported in the 35 years since the dictum of Winterbauer et al3 that one could make a confident clinical diagnosis of SIS. The estimates of the incidence of ADs would have to err by a 1,000-fold order of magnitude to void these conclusions. Nullification of this recommendation on evidentiary grounds would require the demonstration that tissue verification in presumptive S1S identified a substantial number of ADs, and those persons identified with an AD earlier in their course were materially benefited. In this era of runaway health costs, we would like to suggest that skilled clinicians should first weigh the need for tissue confirmation in cases with high pretest probability of S1S.