Recognizing and weighing harms associated with treatment is a core aspect of patient safety. Recently, low-dose computed tomography (LDCT) screening for lung cancer has been promoted by the 20% relative reduction in lung cancer-specific mortality found in a large clinical trial. This study evaluated National Lung Cancer Screening Trial data to determine an estimate of LDCT-detected lung cancer that would not otherwise become clinically apparent—or cancer overdiagnosis. Using these calculations, approximately 20% of cancers detected by LDCT screening represented overdiagnosis. From a research perspective, this study advances our understanding of the measurement of overdiagnosis, and this approach may also be useful for evaluating overdiagnosis of other conditions. A recent AHRQ WebM&M interview with Dr. Rebecca Smith-Bindman discussed radiation safety and the implications of increasing use of CT scans.