BACKGROUND Ultrasonography is the most frequently used clinical tool for the identification, assessment, and follow-up of thyroid nodules. The purpose of this research was to evaluate the value of diagnostic ultrasonography indicators, to obtain rankings of the most valuable indicators in the differential diagnosis of thyroid nodules, and to analyze the optimal diagnostic points and clinical values. METHODS One hundred forty-four patients with 172 thyroid nodules underwent preoperative ultrasonography examinations, including gray-scale ultrasonography (GSUS), color Doppler ultrasonography (CDUS), and contrast-enhanced ultrasonography (CEUS). Fourteen indicators of thyroid nodules on GSUS, CDUS, and CEUS were selected to evaluate all thyroid nodules. The differences between the benign and malignant thyroid nodules in all indicators were analyzed by the chi-squared test; the diagnostic ultrasonography values were obtained by logistic regression; and the optimal diagnostic points were explored by receiver operating characteristic curve analysis. RESULTS Of the 172 thyroid nodules that were surgically removed, 78 were benign and 94 were malignant. Ten indicators of GSUS and CEUS showed significant differences between the benign and malignant nodules (p<0.05), whereas four CDUS indicators had no value. The rankings of the valuable indicators were obtained according to their odds ratios (ORs). The top four indicators were ring enhancement and homogeneity of enhancement on CEUS, and microcalcification and halo on GSUS. These indicators were the most valuable, with ORs of greater than 20 in the differential diagnosis of benign and malignant thyroid nodules. The other six indicators-the relative arrival time of the nodule on CEUS, interior echogenicity on GSUS, peak interior echogenicity on CEUS, shape on GSUS, peak peripheral echogenicity on CEUS, and orientation on GSUS-were also valuable, with ORs less than 20. The areas under the receiver operating characteristic curves for GSUS, CEUS, and the combination of GSUS and CEUS in the diagnosis of thyroid nodules were 0.936, 0.910, and 0.966, respectively. Five positive features of the 10 valuable indicators on GSUS and CEUS defined the cut-off for the diagnosis of malignant thyroid nodules, with a sensitivity of 89.4% (84/94), specificity of 93.6% (73/78), and accuracy of 91.3% (157/172). CONCLUSIONS The ring enhancement and homogeneity of enhancement of thyroid nodules on CEUS and the microcalcification and halo on GSUS were the four most valuable indicators in the differential diagnosis of thyroid nodules. Conjoint analysis of specific features of thyroid nodules on GSUS and CEUS could enhance the diagnostic value of thyroid nodules.