Objective To evaluate the value of high-frequency color ultrasound for different types of thyroid nodules during healthy examinations. Methods A total of 150 subjects with ultrasound diagnosis of thyroid nodule abnormality were enrolled. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ultrasound diagnosis for differentiating benign and malignant thyroid nodules were evaluated with histopathological examinations of surgical thyroid specimens as a gold standard. Results A single thyroid nodule was found in all patients, and histopathological examinations identified 102 benign thyroid nodules and 48 malignant nodules. Microcalcification showed the highest accuracy for prediction of benign and malignant thyroid nodules (98.1%; χ² = 45.67, P = 0.001), followed by taller than wider shape of thyroid nodule (92.1%; χ² = 34.06, P = 0.001), central vascularity (82.0%; χ² = 13.29, P = 0.001), halo (76.0%; χ² = 6.15, P = 0.008) and hypoechogenicity (70.3%; χ² = 10.63, P = 0.001). In addition, ultrasound diagnosis showed a 100.0% sensitivity, a 94.1% specificity, a 88.9% positive predictive value, a 100.0% negative predictive value and a 96.0% accuracy for differentiation between benign and malignant thyroid nodules (χ² = 41.830, P < 0.001). Conclusion High-frequency color ultrasound has a high diagnostic accuracy for differentiating benign and malignant thyroid nodules, and microcalcification and taller than wider shape of thyroid nodule exhibit high values for predicting the malignancy of thyroid nodules.