Achondroplasia (ACH) is a genetic disorder with autosomal dominant inheritance and is the cause of one of the most common forms of short limb dwarfism in humans. Mutations of special sites in the fibroblast growth factor receptor-3 gene (FGFR3) are reported as a cause of ACH, and almost 98% of cases are caused by mutations in nucleotide 1138 (Gly380Arg), with 97% involving a c.1138G>A mutation and 1% involving a c.1138G>C mutation. Therefore, the development of a simple, reliable, and rapid approach for molecular detection of nucleotide 1138 mutations is of great significance for prevention and early diagnosis of ACH. High-resolution melting (HRM) is a new, rapid, and inexpensive molecular detection method that has been generally applied to mutation scanning. In this study, 12 cases of ACH, including 10 sporadic cases and 2 cases in a pedigree, were detected simultaneously using HRM analysis and restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Eleven cases were identified as carrying the c.1138 G>A heterozygous mutation, and one case was identified as carrying the c.1138 G>C heterozygous mutation. Compared with RFLP-PCR, HRM analysis provided a more rapid, simpler, and less expensive approach for detecting the most common FGFR3 mutations carried by patients with ACH.