The aim of the present study was to perform a systematic review of published studies to provide a robust estimation of the use of procalcitonin (ProCT) as a diagnostic marker of medullary thyroid carcinoma (MTC), with particular focus on its specificity and negative predictive value in excluding MTC. A comprehensive computer literature search was conducted to find relevant published articles on the topic. We used a search algorithm based on a combination of the terms ‘medullary,’ ‘thyroid,’ and ‘ProCT.’ The search was updated until February 2015. To expand our search, references of the retrieved articles were also screened. A total of 39 articles were retrieved, of which nine original papers published from 2003 to 2014 were selected for the review. Some of these studies used ProCT in the preoperative diagnosis of MTC, whereas others measured ProCT during the follow-up of patients who had been previously treated for MTC. Other laboratory measurements were performed in some of the included studies. The results of the majority of the studies indicate that ProCT measurement appears to be a very promising and reliable serum marker for the diagnosis of MTC, and it is not inferior to calcitonin (CT). The sample handling is less laborious, and in the few CT-negative cases reviewed, the assay had even greater sensitivity. It would be worthwhile to establish cutoff levels using larger patient series, because we speculate that this assay could potentially replace CT measurement in the future.