Although in common and classic migraine there is platelet activation both during painful attack and headache-free periods, the role of platelets in migraine pathogenesis is not yet understood. Therefore, in order to investigate the relationship between platelets and migraine pathogenesis, β-thromboglobulin (β-TG) and platelet factor four (PF4), both platelet-specific alpha granule proteins, were assayed in a group of patients with classic and complicated migraine before and after administration of an anti-migraine drug, flunarizine, at a dose of 10 mg/daily. Blood samples for β-TG and PF4 assay were collected for ten days in which the patients were headache-free. β-TG and PF4 plasma levels were elevated in all patients in comparison with control subjects. The patients with complicated migraine showed the highest plasma values. During flunarizine treatment β-TG and PF4 levels persisted elevated in all patients, although a slight decrease of β-TG plasma levels was observed. This data confirmed, as our previous works, that classic migraine is characterized by platelet activation “in vivo,” but that this may not be strictly related to migraine pathogenesis.