Objective: To investigate the clinical significance of the BRAF gene mutation in papillary thyroid carcinoma (PTC). Methods: One-hundred and twenty-two eligible PTC patients undergoing surgical treatment within the past 2 years were selected. DNA samples of the patients were extracted from paraffin sections and the V600E mutation of the BRAF gene (BRAFV600E) was detected by fluorescent PCR. The relations of BRAFV600E mutation with clinicopathologic factors and central compartment lymph node metastasis were analyzed. Results: The incidence of BRAFV600E mutation was 69.0% (87/126) in the 126 PTC patients. Univariate and multivariate analysis showed that BRAFV600E mutation was significantly related to lymph node metastasis (P<0.05), and central compartment lymph node metastasis was significantly associated with age, tumor size, tumor stage and BRAFV600E mutation (all P<0.05). Further analysis demonstrated that BRAFV600E mutation had no significant relation with central compartment lymph node metastasis in patients whose tumor size was equal to or less than 10 mm (P>0.05), while among patients with tumor size larger than 10 mm, the incidence of central compartment lymph node metastasis was significantly higher in positive BRAFV600E mutation cases than that in negative BRAFV600E mutation ones (P<0.05). Conclusion: BRAFV600E mutation is an independent predictor associated with aggressive tumor behavior and is an independent predictive factor for central compartment neck dissection. In those cases with positive BRAFV600E mutation, the larger the size of the tumor, the more important it is to perform central compartment neck dissection.