Recent studies highlight cortical demyelinated lesions as a feature of multiple sclerosis (MS) pathology, which has received little attention so far. Here, we describe that cortical plaques are frequent and widespread, in particular in patients with primary or secondary progressive MS. Furthermore, we describe that certain cortical areas, such as the cingulated gyrus, the insular cortex and the temporobasal cortex, are more affected than others. These data indicate that cortical lesions have to be considered as an additional pathological substrate for cognitive dysfunction in MS patients.