Objective: To determine the significance of the A218C polymorphism of the tryptophan hydroxylase (TPH) gene in migraine. Methods: Fifty-nine migraineurs and 62 healthy controls were included in the study, and polymerase chain reaction – restriction fragment length polymorphism assays were used to determine TPH A218C polymorphism. Results: There was no association between TPH gene polymorphism and gender, family history of migraine and epilepsy, or aura. There was no significant difference between the allele frequencies of both groups (p > 0.05). A significant difference was found between the genotypes of the migraineurs and controls regarding the AA genotype. Homozygosity for the C allele or heterozygosity for the A or C was not associated with the occurrence of migraine (p > 0.05), but homozygosity for the A allele was less frequent in the migraineurs (p = 0.02). Conclusion: Since it is unlikely that TPH polymorphism alters serotonin biosynthesis, its association with migraine may be attributed to linkage disequilibrium with a functional variant within the TPH gene or a nearby gene.