However, while these criteria identify a population at risk, the individual predictive value of light microscopic changes is not ideal. Jeremy George, Middlesex, UK, presented intriguing data on this point.7 He presented a surveillance study of “premalignancy” observed by light microscopy of bronchoscopic biopsy specimens. He found that over time some of the severe dysplasias regressed, while some progressed. Cancers developed in some of these sites of severe dysplasia, but not others. Most interesting, several cancers developed in sites within the lung with a normal appearance by white light and Laser Induced Fluorescent Endoscopy bronchoscopy, and also normal by light microscopy. He concluded that the airways in these patients are extremely unstable. This is also evidence that the canonical sequence of metaplasia – dysplasia – carcinoma in situ – invasive cancer is not as linear as initially thought. It is clear that light microscopically observable preneoplastic alterations of bronchial epithelial cells precede only a relatively small fraction of clinical cancers. It is in fact difficult to find adjacent dysplasia in resection specimens. These abnormalities also sometimes regress spontaneously. In addition, while these lesions are highly associated with squamous cell carcinoma (a decreasing subset of non-small cell lung cancer), they are less so for adenocarcinoma or small cell lung cancer, the latter disease also highly smoking related. I feel that smoking causes both dysplasia and cancer, but that these are “true, true, and only partially related.” The most informative investigation would be to study underlying genetic alterations in bronchial epithelial cells independent of light microscopic changes (perhaps, however, focusing on patient populations identified as being at high risk by virtue of the presence of these light microscopic changes). Thus, there should be an increasing emphasis on molecular methods for lung cancer early detection or risk evaluation “unbiased” by light microscopy.