The aim of this study was to evaluate the differences in ultrasonic features of patients with medullary thyroid carcinoma (MTC), papillary thyroid carcinoma (PTC), and benign thyroid nodules. This study included 53 cases of MTC, 151 cases of PTC, and 200 cases of benign thyroid nodule which were pathologically confirmed. There were no significant differences in sex and thyroid gland involvement among the MTC, PTC, and benign thyroid nodule groups. The age among the 3 groups was statistically different (P = 0.002). The TNM stage of MTC was significantly higher than that of PTC (P < 0.001). Compared with PTC, the lesion size, shape, margin, echogenicity, internal nodule component, and blood flow were significantly different in MTC (P < 0.001, P < 0.001, P < 0.001, P < 0.001, P = 0.045, P < 0.001). However, there were no differences in the form of calcification and cervical lymph node involvement between the 2 groups (P = 0.671, P = 0.128). Except for the lesion size and shape (P = 0.068, P = 0.444), MTC group have significant differences in the grade of Thyroid Imaging Reporting and Data System, lesion margin, echogenicity, internal nodule component, calcification, cervical lymph node, and blood flow compared with benign thyroid nodule group (P < 0.001, P = 0.014, P = 0.032, P < 0.001, P < 0.001, P < 0.001). Our data indicate that ultrasound have important value in preoperative diagnosis of MTC. The ultrasonic features of MTC include relatively large nodules, aspect ratio less than 1, smooth edge, solid hypoechoic, microcalcification, and rich blood flow. It is necessary to combine multiple ultrasonic features for the differential diagnosis of MTC, PTC, and benign thyroid nodules.