Migraine often co-occurs with patent foramen ovale (PFO), and some people have suggested surgical closure as an efficient treatment for migraine. Prospective studies, however, do not report radical effect of PFO surgery on migraine. Here, we examined the hypothesis that PFO and migraine may cooccur as two independent manifestations of lateralization defect during embryonic development. We measured the absolute displacement of a midline structure, the pineal gland, on brain scans of 39 migraineurs and 26 controls. We found a significant asymmetry of the pineal gland in migraineurs compared with controls. Our data suggest that migraine's circadian component and its association with PFO may be linked to a lateralization defect during embryogenesis, which could be a result from abnormal serotonin regulation. NeuroReport 19:1351-1353 (c) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.