Purpose To update information regarding the usefulness of computer-aided detection (CAD) systems with a focus on the most critical category, that of missed cancers at earlier imaging, for cancers that manifest as a solid nodule. Materials and Methods By using a HIPAA-compliant institutional review board-approved protocol where informed consent was obtained, 50 lung cancers that manifested as a solid nodule on computed tomographic (CT) scans in annual rounds of screening (time 1) were retrospectively identified that could, in retrospect, be identified on the previous CT scans (time 0). Four CAD systems were compared, which were referred to as CAD 1, CAD 2, CAD 3, and CAD 4. The total number of accepted CAD-system-detected nodules at time 0 was determined by consensus of two radiologists and the number of CAD-system-detected nodules that were rejected by the radiologists was also documented. Results At time 0 when all the cancers had been missed, CAD system detection rates for the cancers were 56%, 70%, 68%, and 60% (κ = 0.45) for CAD systems 1, 2, 3, and 4, respectively. At time 1, the rates were 74%, 82%, 82%, and 78% (κ = 0.32), respectively. The average diameter of the 50 cancers at time 0 and time 1 was 4.8 mm and 11.4 mm, respectively. The number of CAD-system-detected nodules that were rejected per CT scan for CAD systems 1-4 at time 0 was 7.4, 1.7, 0.6, and 4.5 respectively. Conclusion CAD systems detected up to 70% of lung cancers that were not detected by the radiologist but failed to detect about 20% of the lung cancers when they were identified by the radiologist, which suggests that CAD may be useful in the role of second reader. (©) RSNA, 2016.