Objectives This study sought to determine the accuracy of plaque pattern assessment by coronary computed tomography angiography (CCTA) to differentiate between early and advanced atherosclerotic lesions as defined by histology. Background A ringlike attenuation pattern of coronary atherosclerotic plaques termed as napkin-ring sign (NRS) was described in CCTA of patients who had acute coronary syndrome. Methods All procedures were performed in accordance with local and federal regulations and the Declaration of Helsinki. Approval of the local ethics committees was obtained. We investigated 21 coronary arteries of 7 donor hearts. Overall, 611 histological sections were obtained and coregistered with CCTA images. The CCTA cross sections were read in random order for conventional plaque categories (noncalcified NCP, mixed MP, calcified CP) and plaque patterns (homogenous, heterogeneous with no napkin-ring sign non-NRS, and heterogeneous with NRS). Results No plaque was detected in 134 (21.9%), NCP in 254 (41.6%), MP in 191 (31.3%), and CP in 32 (5.2%) CCTA cross sections. The NCP and MP were further classified into homogenous plaques (n = 207, 46.5%), non-NRS plaques (n = 200, 44.9%), and NRS plaques (n = 38, 8.6%). The specificities of NCP and MP to identify advanced lesions were moderate (57.9%, 95% confidence interval CI: 50.1% to 65.6%, and 72.1%, 95% CI: 64.7% to 79.4%, respectively), which were similar to the homogenous and heterogeneous plaques (62.6%, 95% CI: 54.8% to 70.3%, and 67.3%, 95% CI: 58.6% to 76.1%, respectively). In contrast, the specificity of the NRS to identify advanced lesions was excellent (98.9%, 95% CI: 97.6% to 100%). The diagnostic performance of the pattern-based scheme to identify advanced lesions was significantly better than that of the conventional plaque scheme (area under the curve: 0.761 vs. 0.678, respectively; p = 0.001). Conclusions The assessment of the plaque pattern improves diagnostic accuracy of CCTA to identify advanced atherosclerotic lesions. The CCTA finding of NRS has a high specificity and high positive predictive value for the presence of advanced lesions.