In lung cancer, early detection and diagnosis is of paramount importance. In 2011 the National Lung Screening Trial (NLST) demonstrated the effectiveness of computed tomography (CT) screening for lung cancer in reducing mortality, and results from other ongoing trials are expected to be published in the near future. A topic that has not been widely researched to date, however, is the cause for screening failure and missed lung cancers. In this issue of European Radiology, Scholten et al. describe a number of causes for false-negative screens. Some of the implications for CT screening and nodule management raised by this report are discussed. Key Points • Many causes exist for missed lung cancers in CT screening trials • Endobronchial structures, the hila and mediastinum are blind spots on screening CTs • The management of atypical nodular opacities on thoracic CT may be challenging.