Grey matter (GM) damage in Multiple Sclerosis (MS) occurs largely independent of white matter (WM) lesions and shows stronger correlation with clinical parameters than WM damage but no clear pattern of GM atrophy distribution has emerged in the literature. We used Signed Differential Mapping (SDM), a novel neuroimaging meta-analytical method, to assess global and regional GM volume differences in MS. Meta-regression methods were used to explore potential effects of disease duration and degree of functional disability. We found a highly localized pattern of regional GM volume loss in Relapsing Remitting MS involving bilateral thalamus, basal ganglia structures, pre/postcentral regions and cingulate gyrus. These results remained largely unchanged after subgroup and sensitivity analyses. Furthermore, GM volume loss in left pre/postcentral regions correlated with increasing functional disability in MS. These results demonstrate that GM atrophy occurs as a regional rather than global process in MS, and that functional disability is specifically associated with atrophy of the left pre/post central gyrus. Further investigation is needed to determine whether these structures are targeted by neurodegenerative processes and to establish their clinical and neurocognitive correlates.