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High-resolution melting (HRM) is one of the widely used methods for mutation detection. Sometimes, mutations which are rare but clinically important may not be detected. Thus, increasing sensitivity of HRM based mutation detection method is essential. This study was particularly aimed to establish HRM based mutation detection method with improved sensitivity. However, we had taken an attempt to detect the mutations in transcription factor 7-like 2 (TCF7L2) gene by HRM analysis but we experienced poor sensitivity in mutation detection. Hence, we tried to increase the sensitivity of HRM by adding formamide and dimethyl sulfoxide (DMSO). We used the final concentration of formamide and DMSO at 0.2% and 7%, respectively and found that formamide had better efficacy in increasing HRM sensitivity than DMSO. [ J Adv Biotechnol Exp Ther 2019; 2(2.000): 51-54]