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Purpose: The BRAFV600E mutation represents a novel indicator of the progression and aggressiveness of papillary thyroid carcinoma (PTC). The purpose of this study was to determine the clinical significance of free circulating mutant BRAFV600E in predicting the advanced disease of PTC. Materials and Methods: Seventy seven matched tumor and plasma samples obtained from patients with both benign and PTC were analyzed for BRAFV600E mutation using a peptide nucleic acid (PNA) clamp real-time polymerase chain reaction (PCR). Results: The BRAFV600E mutationwas absent in tumor DNA samples obtained from patients with benign follicularadenomas or adenomatous goiter. In contrast, 49 of 72 (68.1%) PTC tumors were positive for the BRAFV600E mutation. Among them, 3 (6.1%) patients with PTC were positive for BRAFV600E mutation in plasma and tumor. However, all 3 patients(100%) had lateral lymph node and lung metastasis. Conclusion: These findingssuggest that the BRAFV600E mutation can be detected using a PNA clamp real-time PCR in the blood of PTC patients with lung metastasis. Future studies are warranted to determine clinical significance of serum BRAFV600E mutation in large prospective studies.