Single nucleotide polymorphisms (SNPs) are new generation markers. An open question in research on SNPs is how to find novel SNPs in a nature population. To this end, we developed an approach of high-throughput genotyping by applying the temperature-modulated heteroduplex analysis (TMHA) based upon ion-pair reversed-phase high-performance liquid chromatography. This approach allowed a very efficient resolution of identically sized PCR products with a single nucleotide change. This approach was also known as denaturing high-performance liquid chromatography (DHPLC). However, the terms of both TMHA and DHPLC should be considered carefully. The term of DHPLC may lead to confusion in annealing and denaturing. Since TMHA can be carried out using gel electrophoresis and HPLC, there is a need to distinguish HPLC from gel electrophoresis. Therefore, we suggest a new term for this technology, which is temperaturemodulated high-performance liquid chromatography (TmHPLC). This term not only provides a clear definition for this new method, but also includes both TMHA and HPLC. More importantly, TmHPLC implies that the temperature in HPLC is modulated according to Tm of the DNA fragments. Our results show that TmHPLC is a sensitive, accurate and cost effective approach to screening sequence variation in human genome.