A potential overlap between bipolar disorder (BD) and borderline personality disorder (BPD) has been recently proposed. We aimed to assess similarities and differences of brain structural features in BD and BPD. Structural magnetic resonance imaging (MRI) was performed in 26 inpatients with BPD, 14 with BD, and 40 age-and sex-matched healthycontrols (HC). Voxel-based morphometry analysis with Statistical Parametric Mapping (SPM) was used to localize and quantify gray (GM) and white matter (WM) abnormalities in BD and BPD compared to HC and to identify those specifically affected in each patient group. Region of interest (ROI)-based analyses were also performed for confirmation. GM density changes in BD are significantly more diffuse and severe than in BPD, as demonstrated in both SPM- and ROI-based analyses. The topography of GM alterations showed some regions of overlap, but each disorder had specific regions of abnormality (involving both cortical and subcortical structures in BD, confined mainly to fronto-limbic regions in BPD). WM density changes were less pronounced in both conditions and involved completely different regions. Although BPD and BD show a considerable overlap of GM changes, the topography of alterations is more consistent with the separate conditions hypothesis and with the vulnerability of separate neural systems.