Calcitonin (Ctn) measurement in patients with thyroid disease could potentially increase the detection rates of medullary thyroid carcinoma (MTC) but remains a controversial issue. The aim of this study was to evaluate routine preoperative Ctn measurements. Methods: All patients with thyroid surgery documented in the prospective StuDoQ|Thyroid registry between 03/2017 and 09/2020 were included. Cutoff levels for Ctn were determined with ROC analyses to assess the preoperative diagnosis of MTC in subgroups for females and males. Findings: In 29.590 of 39.679 patients (75%) participating in the registry, routine preoperative Ctn testing was performed. In 357 patients (227 females, 130 males) histopathology confirmed MTC with a mean tumor size of 14.7 mm (± 12.43). Biochemical cure was achieved in 71.4% of the patients. Ctn levels between 11 and 20 pg/ml were seen in 2.6% of the patients, and only 0.7% of the patients had Ctn levels above 21 pg/ml. Cutoff levels for the diagnosis of MTC were 7.9 pg/ml for females and 15 pg/ml for males (p <0.001). The sensitivity and specificity for females were 95% and 98%, and 96% and 97% for males, respectively. Conclusion: Routine Ctn testing is a reliable predictor for MTC and provides the opportunity for earlier thyroidectomy before lymph node metastases occur, resulting in a better prognosis. Females with Ctn levels >7.9 pg/ml and males >15 pg/ml without any other extrathyroidal sources for an elevated Ctn should be monitored. Thyroid surgery should be considered if Ctn levels are increasing, or ultrasound detects suspicious thyroid lesions.