This study was designed to explore differences in the ultrasonographic characteristics of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC). This study included 35 cases of MTC and 96 cases of PTC that were surgically and pathologically confirmed. Preoperative ultrasound images were retrospectively reviewed by two physicians (with 5 years’ experience in thyroid ultrasound) under the premise of unknown pathological results. Various ultrasonic features of nodules were assessed objectively. The clinical features of components were determined by other physicians. Age, sex, unilateral or bilateral involvement of thyroid gland, lesion size, margin, shape, echogenicity, calcification, intranodular blood flow, cervical lymph node, and tumor node metastasis (TNM) stage were compared between MTC and PTC groups. Age, sex, involvement of the thyroid gland, margin, and calcification were similar for the MTC and PTC groups. Compared with the PTC group, the lesion size in the MTC group was significantly larger (P < 0.001). A taller-than-wide shape (aspect ratio > 1) was significantly less likely in the MTC group than the PTC group (P < 0.001). A mixed echogenicity was significantly more common in the MTC group than the PTC group (P = 0.003). The MTC group had significantly enhanced intranodular blood flow (P < 0.001). The TNM stage of the MTC group was significantly higher than that of PTC group (P = 0.001). Medullary thyroid carcinomas differ significantly from PTCs in lesion size, shape, echogenicity, and intranodular blood flow.