Cancer screening measures generally are accepted for cervical, breast, and colon cancer. With prostate cancer screening, the practice is used broadly, but the evidence for this approach is not established clearly. The aggregate clinical experience with these screening procedures provides a useful precedent to consider in designing a new approach to lung cancer screening. For instance, formidable logistic issues exist in responsibly evaluating the vast at-risk population for lung cancer. Obvious issues include the needs for cost-economy and precise classification procedures. In the field of cervical cancer screening, recent developments in automated image analysis highlight the potential for improving the precision of diagnosis by moving beyond traditional manual cytomorphologic evaluation. The authors have outlined how the overexpression of hnRNP A2/B1 was associated significantly with the eventual development of lung cancer, as corroborated by several independent studies. In discussing this marker, they reviewed several issues with relevance to the general challenge in using biomarkers as screening tools for lung cancer. The experience with cervical cancer screening informs the development of a cellular diagnostic screening platform for lung cancer. Issues such as optimized cell preparation, reproducibility, and assay precision are fundamental to the success of the platform for lung cancer detection. The recent Institute of Medicine study of health care delivery provides an excellent point of departure in outlining the global infrastructure that will be necessary in the evolution of a prevention-oriented lung cancer care system. The power of early detection in saving lives from cancer is reflected in the fact that more people die from a single cancer without any validated screening tool (i.e., lung cancer) than die from the aggregate of the four other major cancers, including breast cancer, colon cancer, prostate cancer, and cervical cancer cases--which all have more established early detection approaches. New technologies may provide an opportunity to engage lung cancer routinely at a fundamentally early stage in its natural history, which may provide an opportunity for clinicians to reconsider what may be the best way to manage lung cancer. Further sustained efforts will be required to define the true value of these new approaches through clinical trials as the specialty moves responsibly to routine preventative care of individuals at risk for lung cancer.