Recurrent aphthous stomatitis (RAS) has a multifactorial etiopathogenesis, an interaction between predisposing factors and/or systemic conditions and immunological components in genetically predisposed subjects. The Mediterranean fever (MEFV) gene has already been identified as being responsible for familial Mediterranean fever. Because the association betweenMEFVgene mutations and Behçet's disease has been reported before in several studies, we considered that the role ofMEFVgene mutations should be studied in patients with RAS, because of the clinical similarities of both diseases. The aim of this study was to explore the frequency and clinical significance ofMEFVgene mutations in a cohort of Turkish patients with RAS. The study population comprised 100 unrelated patients with a clinical diagnosis of RAS and 156 healthy controls. Genomic DNA was isolated and genotyped using polymerase chain reaction and restriction fragment length polymorphism for the fourMEFVgene mutations (M694V, M680I, V726A and E148Q). There were statistically significant differences of theMEFVgene mutation carrier rates and allele frequencies between RAS patients and healthy controls (P= 0.042, odds ratio [OR] = 1.9, 95% confidence interval [CI] = 1.01–3.41; andP= 0.039, OR = 1.8, 95% CI = 1.02–3.14, respectively). Even if it is not statistically significant, the E148Q allele frequency was higher in patients with RAS than the control group. A statistically significant increased prevalence ofMEFVvariants in RAS patients was found. This is the first study to report that missense mutations ofMEFVis associated with RAS in the Turkish population.