Background: Poor prognosis of medullary thyroid cancer (MTC) with suspicious ultrasound (US) features has been reported. The aim of the study was to investigate the association between preoperative US presentation and aggressiveness features of MTC. Also, US features of MTC were compared with those previously reported. Methods: Study group comprised 134 MTC from nine different centers. Based on US presentation the nodules were stratified in “at risk for malignancy” (m-MTC) or “probably benign” (b-MTC) lesions. Results: Eighty nine (66.4%) m-MTC and 45 (33.6%) b-MTC were found. Metastatic lymph nodes (p = 0.0001) and extrathyroid invasiveness (p < 0.0001) were more frequent in m-MTC. There was statistically significant correlation (p = 0.0002) between advanced TNM stage and m-MTC with an Odds Ratio 5.5 (95% CI 2.1–14.4). Mean postsurgical calcitonin values were 224 ± 64 pg/ml in m-MTC and 51 ± 21 in b-MTC (p = 0.003). Conclusions: This study showed that sonographically suspicious MTC is frequently associated with features of aggressiveness, suggesting that careful preoperative US of MTC patients may better plan their surgical approach. Keywords: Medullary thyroid cancer, Ultrasonography, Histology, Thyroid nodule