This study was a well-performed evaluation of a pertinent question. However, interpretation of these results first requires the reader to determine the validity of the reported differences in the characteristics and natural history of the groups studied, and we must evaluate whether the differences are suggestive enough to be used as a surrogate marker of differences in tumor biology. When assessing the validity of the reported differences, a few things should be considered. Patient characteristics—age, sex—were clearly different between the groups studied. Internally, the self-reported nature of smoking status could affect validity. Externally, the population studied appears different than commonly encountered in practice, with more women than men reported in the current smoking group as well as the never smoking group. All factors that could influence the natural history were not considered, the most important of these being performance status and treatments received. It is well established that these factors are important determinants of survival.9–10 It is also reasonable to postulate that they may differ between active smokers and never-smokers. Other prognostic factors, including small differences in stage distribution as well as differences in the proportion of bronchoalveolar cell histology,11and sex, were well described in the study and controlled for in multivariate analyses. Including former smokers, although adding complexity, may have influenced the conclusions drawn about the meaning of apparent differences in natural history. Thus, this study is unable to stand alone to establish differences in tumor biology, but must be evaluated in the context of other work in this area. Assuming the above points do not influence the results, it is not unreasonable to suspect that differences in natural history are related to differences in tumor biology; in this regard, the current study is in keeping with others who have evaluated similar epidemiologic questions.12 There is also a growing body of literature on differences in tumor biology between smokers and never-smokers.