Objectives To estimate the ability to discriminate between benign and malignant adnexal masses of subjective assessment, two International Ovarian Tumor Analysis (IOTA) logistic regression models, LR1 and LR2, the IOTA simple rules and the risk of malignancy index (RMI) in ovarian masses of different size. Methods We used a multicenter IOTA database of 2445 patients with at least one adnexal mass, i.e. the database previously used to prospectively validate the diagnostic performance of LR1 and LR2. The masses were categorized into three subgroups according to their largest diameter: small tumors (diameter <4 cm; n= 396), medium sized tumors (diameter 4-9.9cm, n= 1457) and large tumors (diameter >10 cm, n = 592). Subjective assessment, LR1 and LR2, the simple rules and the RMI were applied to each of the three groups. Sensitivity, specificity, positive and negative likelihood ratio (LR+, LR-), Diagnostic Odds Ratio (DOR), and area under the receiver operating characteristic curve (AUC) were used to describe diagnostic performance. A moving window technique was applied to estimate the effect of tumor size as a continuous variable on the AUC. The gold standard was the histological diagnosis of the surgically removed adnexal mass. Results The rate of invasive malignancy was 10% in the small tumors, 19% in the medium sized tumors and 40% in the large tumors; 11% of the large tumors were borderline tumors versus 3% and 4% of the small and medium sized tumors. The type of benign histology also differed between the three subgroups. For all methods, the sensitivity with regard to malignancy was lowest in the small tumors (56-84% vs. 67-93% in medium sized tumors and 74 - 95% in large tumors), while the specificity was lowest in the large tumors (60-87% vs. 83-95% in medium sized tumors and 83-96% in small tumors); the DOR and the AUC were highest in the medium sized tumors. The AUC was largest in tumors with a largest diameter 7-11 cm. Conclusions: Tumor size affects the ability of subjective assessment, LR1 and LR2, the IOTA simple rules and the RMI to correctly discriminate between benign and malignant adnexal masses. This is likely to be explained at least partly by differences in histology between tumors of different size. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.