We previously reported that dysfunctions in the autonomic nervous systems of patients with migraines occur not only in the brain, but throughout the whole body. Serotonin and neuropeptides are also known to have important roles in the pathophysiology of migraine. With this background in mind, we analyzed human lymphoblast cell lines from migraine with aura (MwA) patients to investigate the pathophysiology of migraine. The characteristics of these lymphoblasts and the involvement of the lymphoblasts in serotonin metabolism were examined. The lymphoblasts expressed serotonin receptors as well as some enzymes related to serotonin metabolism. The serotonin level in the MwA lymphoblasts was higher than that in the control cells. However, serotonin uptake into the lymphoblasts in MwA patients was similar to that in the control subjects. These findings suggest that lymphoblasts in MwA patients have altered levels of serotonin metabolism. Moreover, we propose that this lymphoblast cell system could serve as a novel modality for migraine research.