Abstract. The diagnostic value of contrast-enhanced ultrasound (CEUS) or real-time elastography (RTE) alone, as well as a combination of CEUS and RTE, in distinguishing benign from malignant thyroid nodules was investigated. Between August 2012 and June 2014, a total of 97 consecutive patients (50 male and 47 female patients; mean age, 48.6±12.4; age range, 27-70 years) with thyroid nodules referred for surgical treatment were examined by CEUS and RTE. The final diagnosis was obtained based on histological findings. Image analysis of the CEUS and RTE scans was performed. Considering the postoperative pathological results as the golden standard, a receiver operating characteristic (ROC) curve was constructed. Subsequently, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of CEUS alone, RTE alone and CEUS + RTE combination were calculated. Pathological examination showed 66 papillary carcinomas and 43 benign lesions, including 21 adenomas and 22 nodular goiters. The sensitivity, specificity, PPV, NPV and accuracy of CEUS were 81.82, 90.70, 93.10, 90.70 and 85.32%, respectively. In the case of RTE, the sensitivity, specificity, PPV, NPV and accuracy were 80.30, 88.37, 91.38, 88.37 and 83.49%, respectively. Furthermore, the combination of CEUS + RTE had a sensitivity of 95.45%, specificity of 95.35%, PPV of 96.92%, NPV of 95.35% and accuracy of 95.41%. Therefore, the CEUS + RTE combination showed a significantly higher sensitivity and specificity compared with CEUS or RTE alone (all P<0.05). Based on ROC analysis, the area under the curve (AUC) for CEUS, RTE and CEUS + RTE combination was 0.883, 0.863 and 0.959, respectively. The AUC of RTE alone was significantly lower compared with that of the CEUS + RTE combination. In conclusion, our results demonstrate that CEUS + RTE combination significantly increases the diagnostic performance for differential diagnosis of malignant and benign thyroid nodules compared with CEUS or RTE alone.