Objective: To investigate the value of serum calcitonin (Ct) detection for diagnosis of medullary thyroid carcinoma (MTC) in patients with thyroid nodules. Methods: The clinical data of 1 922 patients admitted to the Department of Thyroid Surgery, the First Affiliated Hospital of Zhengzhou University due to thyroid nodules and undergoing surgical treatment from October 2016 to August 2017 were retrospectively analyzed. All patients underwent routine serum Ct detection before operation, and had definite postoperative pathological diagnosis. The relationship between Ct level and MTC was analyzed, and the diagnostic efficiency of Ct for MTC was evaluated by receiver operating characteristic curve analysis. Results: In the 1 922 patients with thyroid nodules, 12 cases (0.62%) were newly diagnosed as MTC. In 155 patients with preoperative Ct value ranging from 10 to 100 pg/mL, 12 patients with preoperative Ct value ranging from more than 100 to 500 pg/mL and 10 patients with preoperative Ct value more than 500 pg/mL, MTC was diagnosed in one case (0.65%), one case (8.33%) and 9 cases (90.00%), respectively. In the 9 MTC patients with preoperative Ct value more than 500 pg/mL, 8 cases (88.89%) had different levels of cervical lymph node metastasis. The cut-off value of serum Ct for diagnosis of MTC was 258.5 pg/mL, with a sensitivity of 90.91% and a specificity of 96.99%. Conclusion: Routine preoperative serum Ct detection is helpful for the early diagnosis of MTC, and it has great importance in patients for receiving thorough surgical resection and avoiding repeated operation.