Migraine is a common neurological disease in the population and the most associated headache with mood disorder. Although the relationship between migraine and depression is well known, the reverse correlation between depression and migraine was observed but not well understood. The tight relationship between the two disturbances is also suggested by the efficacy of antidepressants for migraine treatment. Starting from these observations, we can presume that both migraine and depression have overlapping biological bases. The main target of antidepressant treatments belonging to the serotonin selective reuptake inhibitors (SSRI) type is the serotonin transporter (SERT); a well-studied polymorphic variant, in the promoter region of the gene (SERTPR), has been demonstrated to influence the availability of serotonin in the synaptic cleft. So, our group studied the possible role of the SERT as a risk factor, both for migraine and mood disorders, in a sample of 96 patients affected by both pathologies.