The objective of our study was to determine significant CT findings for the differentiation of biliary cystic neoplasms from simple hepatic cysts and to assess whether radiologists' performance for the differentiation is improved with the knowledge of significant CT criteria. Review of surgical and pathologic records identified 25 patients with pathologically proven biliary cystic neoplasms (biliary cystadenomas [n = 8], biliary cystadenocarcinomas [n = 4]) or simple cysts [n = 13]). Two radiologists retrospectively reviewed CT images in consensus for the location, size, and outer margin of the lesion and for the presence of an internal septum, upstream bile duct dilatation, a transient hepatic attenuation difference (THAD), calcifications, a mural nodule, three or more other cysts, and a thick septum or outer wall. Individual CT findings considered significant for the differentiation were determined using univariate statistical analyses. Then, two successive review sessions for the differentiation between the two disease entities were independently performed by two other reviewers using a 4-point confidence scale. At the first session, no information was provided to reviewers for differentiation. At the second session, however, the reviewers were told of the results of univariate analyses. Radiologists' performance was evaluated using pairwise comparison of receiver operating characteristic (ROC) curves. The mean size of biliary cystic neoplasms (9.5 cm) was not significantly different from that of simple cysts (11.2 cm). The presence of upstream bile duct dilatation achieved the highest specificity (100%) for the differentiation of biliary cystic neoplasms from simple cysts, followed by THAD (84.6%), lesion location at the left lobe (76.9%), and coexistence of fewer than three other cysts (69.2%). The area under the curve of reviewers 1 and 2 significantly increased from 0.686 and 0.654 to 0.997 and 0.936, respectively, when the reviewers knew the information about the significant CT criteria (p = 0.003 and p = 0.008, respectively). Upstream bile duct dilatation, lesion location at the left hepatic lobe, fewer than three coexistent cysts, and THAD were found to be highly suggestive CT findings for the differentiation of biliary cystic neoplasms from simple hepatic cysts. Radiologists' performance was significantly improved with the knowledge of these highly suggestive CT criteria.