AbstractObjectivesMigraine is a common, multifactorial disorder. The exact pathomechanism of migraine remains unclear. Studies have revealed changes in serum prolactin (PRL) levels in relation to migraine, although the results have been inconsistent. The present case‐control study assessed the serum level of prolactin in migraine patients.Materials and methodsIn this case‐control study, participants were divided into chronic migraine (CM;n= 39), episodic migraine in ictal (during an attack), and interictal (between attacks) phases (n= 63,n= 37, respectively) along with 30 age‐ and sex‐matched headache‐free controls. After obtaining demographic, anthropometric data, and headache characteristics, blood samples were gathered and analyzed to evaluate the serum levels of prolactin (ng/mL).ResultsA significant difference was observed between the control, CM, and ictal EM, and interictal EM groups. The mean ± SD serum prolactin levels of the chronic migraineurs (1.82 ± 0.94) and those with ictal EM (1.93 ± 1.70) were comparable and were significantly higher than for interictal EM patients (0.82 ± 0.46) and the headache‐free control subjects (0.49 ± 0.15;p< .001). Although the mean serum concentration of prolactin for the interictal EM group tended to be higher than for control individuals, this difference was not statistically significant. The Spearman's correlation test also showed significant correlations between the serum prolactin levels and the number of headaches days among migraineurs.ConclusionThe findings suggest that there might be an association between increased prolactin concentrations and migraine headache induction and progression. Further detailed and well‐designed studies are needed to confirm the importance of serum prolactin levels in the pathogenesis of migraine headaches.