Mandibular prognathism (MP) is a common craniofacial disorder of Class III malocclusion that causes esthetic and functional problems. Class III malocclusion diversity is influenced by both environmental and genetic factors. Single nucleotide polymorphisms (SNPs) in genes involved in craniofacial morphogenesis, bone and cartilage development, and metabolism, could play a role as predisposing factors. The present study aimed to establish a potential association between MATN1 -1878 A>G (rs1149048), MYO1H 1001 C>T (rs3825393), and BMP-4 538 A>G (rs17563) SNPs and MP in Serbian population.The study included 110 participants: 55 patients with Class III malocclusion diagnosed with MP and 55 with Class I malocclusion. The 3 SNPs were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method.The genotype frequency of MYO1H showed a highly significant difference between patients and controls. Heterozygous carriers of the T allele had an almost 3-fold increase in odds for the development of MP (odds ratio, 2.79; 95% confidence interval, 1.26-6.19; P = 0.010). No association could be established between MATN1 and BMP-4 polymorphisms and MP.Our results support the concept of gene polymorphisms as risk modulators in mandibular prognathism development, although only the association between MYO1H and MP was found in Serbian patients with Class III malocclusion.