Migraine patients with multiple brain white matter hyperintensities (WMHs) may represent a diagnostic challenge. Using double inversion recovery (DIR) imaging, we studied whether cortical lesions (CLs) could be seen in these patients. Approval of the institutional review boards and written informed consent were obtained from each participant. CLs and WM lesions were assessed on brain scans from 32 migraine patients with WMHs (17 patients with and 15 without aura), and in two control groups, consisting of 15 relapsing-remitting multiple sclerosis (RRMS) patients and 20 healthy controls, matched for age and gender. By definition, brain WM lesions were detected in all migraine and RRMS patients. The number and volume of WM lesions were lower in migraine versus RRMS patients (p < 0.0001). No CLs were identified in migraine patients and healthy controls, whereas 20 CLs were seen in 9 (60 %) RRMS patients. The application of DIR imaging to assess focal cortical involvement seems to be useful in the diagnostic workup of patients with WMHs of unknown etiology, including those with migraine.