We investigated the possible association of serotonin (5-HT) 2A receptor gene A-1438G polymorphism in Japanese patients with migraine. Genotyping of 5-HT(2A) A-1438G polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism in patients with migraine (male 17 : 3 with aura and 14 without aura, female 65 : 17 with aura and 48 without aura) and controls (male 31, female 84). The distribution of 5-HT(2A) A-1438G genotype frequency between migraine patients and controls did not differ. These results suggest that the A-1438G polymorphism of the 5-HT(2A) receptor gene is not a direct risk factor for migraine; however, the incidence of the A/A genotype between migraine with aura (MA) and without aura (MO) was significantly different. The 5-HT(2A) A-1438G polymorphism may be involved in determining the subtypes of migraine in Japanese.