<b><i>Background:</i></b> Migraine and nocturnal enuresis are highly prevalent disorders with striking similarities. Both have unknown pathophysiology and are considered multifactorial, with neurobiological, genetic, and behavioral aspects involved. Interestingly, the same neurological structures thought to be involved in the pathogenesis of migraine are also thought to be involved in nocturnal enuresis. Few studies, however, have addressed these conditions as related. The aim of this study was to evaluate the antecedent of nocturnal enuresis in a large consecutive series of adolescents with migraine as compared to controls. <b><i>Methods:</i></b> A total of 151 subjects were evaluated; 50 had episodic migraine, 50 had chronic migraine, and 51 were control subjects. All patients were submitted to a detailed questionnaire addressing epidemiological and clinical aspects. <b><i>Results:</i></b> There was a strong correlation between the clinical history of nocturnal enuresis and the diagnosis of migraine. <b><i>Conclusion:</i></b> Our study showed that nocturnal enuresis is a precursor of migraine and a migraine comorbid condition. These results support a pathophysiological linkage between the two conditions.