<i>Background /Aims:</i> Up to more than 50% of cryptogenetic stroke patients and patients with migraine with aura (MA) are found to have a right-to-left shunt (RLS), which is usually due to a patent foramen ovale. Moreover, both MA and stroke are cardinal features of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL). <i>Notch3</i> mutations have been suggested to induce an abnormally high incidence of atrial septal defects in a family harbouring an Arg141Cys pathogenetic mutation. We sought to determine the prevalence of RLS in CADASIL patients with different <i>Notch3</i> mutations, both with and without migraine as a clinical feature. <i>Methods:</i> Subjects with a molecular diagnosis of CADASIL were tested for the presence of an RLS by means of contrast-enhanced transcranial Doppler (TCD). The diagnosis of migraine was made according to the 2004 International Headache Classification. <i>Results:</i> Sixteen CADASIL patients were tested; 6 had MA. Four patients displayed an RLS on contrast-enhanced TCD examination. Three of these patients had MA. Both patients with Arg141Cys displayed a large RLS. <i>Conclusion:</i> We conclude that RLS is not necessarily linked to CADASIL as a comorbidity factor. Nevertheless, there could be a relation between RLS and specific <i>Notch3</i> mutations, such as Arg141Cys.