Background/Aim: This study compared the efficacy of PANAMutyper™, a novel technology that integrates PNAClamp™ and PANA S-Melting™, and PNAClamp™ alone for the detection of EGFR mutations in lung cancer patients. Materials and Methods: PANAMutyper™ and PNAClamp™ were used to assess the EGFR mutation status in tissue, cell block, pleural effusion, and blood samples of 90 lung cancer patients with malignant pleural effusion. Results: PANAMutyper™ detected more EGFR mutations than PNAClamp™, especially in body fluids (pleural effusion and serum). Patients with additional EGFR mutations detected using PANAMutyper™ had a favorable response to EGFRtyrosine kinase inhibitor (TKI) treatment. Conclusion: The diagnostic performance of PANAMutyper™ was superior to that of PNAClamp™ for the detection of EGFR mutations. It was also better at identifying lung cancer patients with malignant pleural effusion who were likely to benefit from EGFR-TKI treatment.The use of molecular agents targeting the epidermal growth factor receptor (EGFR) is important in the treatment of advanced non-small cell lung cancer (NSCLC) (1-3).Multiple prospective clinical trials have demonstrated that patients with advanced NSCLC harboring activating mutations in the EGFR gene show improved objective response rates and progression-free survival (PFS) when treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs) (1,2,(4)(5)(6)(7)(8). Therefore, molecular testing for EGFR mutations has become essential for predicting whether a patient will benefit from EGFR-TKI targeted therapy (9).Previously, we compared peptide nucleic acid (PNA) clamping with direct sequencing for the detection of EGFR and K-RAS mutations. Our results showed that PNA clamping has a better diagnostic performance and higher clinical significance (10, 11).