OBJECTIVES: The high cost of preoperative molecular testing remains a significant barrier to their widespread clinical use. This prospective study aims to investigate the clinical applicability of the ThyroSCAN PanelChip, a qPCR-based method, for preoperative BRAF V600E testing in thyroid nodules. MATERIALS AND METHODS: Adult patients undergoing fine-needle aspiration cytology in outpatient settings between April 2023 and June 2024 were enrolled, and molecular testing was performed on aspiration samples. For patients who proceeded to thyroidectomy, postoperative histopathological findings were compared with preoperative cytology and molecular results. Immunohistochemical VE1 staining on pathology specimens served as the gold standard to validate accuracy. A best-estimate approach was also employed to expand the evaluation, including presumed BRAF V600E-negative cases, such as RAS-positive specimens and benign lesions. RESULTS: Among 73 patients who underwent thyroidectomy and were included in the analysis, preoperative molecular testing identified BRAF mutations in 22 patients, detected the wild-type gene in 39 and classified 12 as inaccessible due to insufficient DNA extraction. For the 38 patients with both preoperative genetic results and VE1 staining, performance metrics were: positive predictive value = 95.5%, negative predictive value = 75.0%, accuracy = 86.8%, sensitivity = 84.0% and specificity = 92.3%. Under the best-estimate approach, metrics improved to positive predictive value = 95.5%, negative predictive value = 89.5%, accuracy = 91.7%, sensitivity = 84.0% and specificity = 97.1%. CONCLUSION: These findings demonstrate that ThyroSCAN PanelChip effectively identifies BRAF V600E mutations in thyroid nodules using residual thyrocytes from fine-needle aspiration samples.