The purpose of this prospective study was to compare the accuracy of computed tomography (CT) and transvaginal ultrasonography in the differential diagnosis of persistent cystic ovarian lesions. The candidates for this study were 161 premenopausal non-pregnant women with an adnexal mass. After a 3-month follow-up, 83 masses persisted and were examined by both techniques before surgery. We also evaluated the CA-125 plasma levels. The CT and ultrasonographic diagnoses were then compared with the histopathological diagnosis. The overall agreement between the test results and the actual outcome was calculated by means of the kappa statistic. Transvaginal ultrasonography has a closer accuracy in the diagnosis of serous cysts and serous cystadenoma, ovarian carcinoma and endometrioma (value of kappa: 0.78, 0.73 and 0.80, respectively) than CT, even if the latter is associated with clinical and biochemical parameters such as patient's age and CA-125 plasma levels. Only in the diagnosis of cystic teratoma, is transvaginal ultrasonography less accurate than CT. In conclusion, in premenopausal women, transvaginal ultrasonography remains a cost-effective method in the diagnosis of most cystic ovarian lesions.