<b><i>Background</i></b> Total thyroidectomy and cervical lymph node (LN) dissection is generally recommended in patients with medullary thyroid carcinoma (MTC). However, there is no clear evidence for whom to perform prophylactic lateral neck dissection in MTC patients without evident lateral cervical lymph node (LCLN) metastasis in preoperative images. This study evaluated the preoperative features for predicting the LCLN metastasis of MTC. <b><i>Methods</i></b> We included 26 MTC patients with LCLN metastasis at initial surgery (N1b group) and 47 MTC patients without any LN metastasis or recurrence of disease (N0-NED group). We evaluated the association between LCLN metastasis and preoperative clinical and sonographic characteristics (size, location, solid component, shape, margin, echogenicity, calcification, and subcapsular location of the tumor). <b><i>Results</i></b> There were no significant differences in age and sex between the N1b and N0-NED groups. Preoperative serum levels of calcitonin (Ctn) above 65 pg/mL were associated with LCLN metastasis (p < 0.001). In preoperative neck ultrasonography (US), patients in the N1b group were more commonly found with a larger tumor (>1.5 cm) of irregular shape with a spiculated margin and a subcapsular location than those in the N0-NED group (p = 0.029, p < 0.001, p < 0.001, and p < 0.001, respectively). Increases in the number of these LCLN metastasis-related features were significantly associated with higher risk for LCLN metastasis (p < 0.001). The presence of two or more predictors was an appropriate cut-off point for predicting LCLN metastasis of MTC with 73.1% sensitivity and 91.5% specificity. <b><i>Conclusions</i></b> MTC tumors with high preoperative Ctn levels (>65 pg/mL), larger size (>1.5 cm), irregular shape, spiculated margins, and subcapsular locations in the neck US are at higher risk for LCLN metastasis. MTC patents with less than two predictors might be suitable for treatment without prophylactic LCLN dissection.