Glioblastoma (GBM) and meningothelial meningioma (MM) are the most frequent malignant and benign brain lesions, respectively. Mechanical cues play a major role in the progression of both malignancies that is modulated by the occurrence of aberrant physical interactions between neoplastic cells and the extracellular matrix (ECM). Here we investigate the nano-mechanical properties of human GBM and MM tissues by atomic force microscopy. Our measures unveil the mechanical fingerprint of the main hallmark features of both lesions, such as necrosis in GBM and dural infiltration in MM. These findings have the potential to positively impact on the development of novel AFM-based diagnostic methods to assess the tumour grade. Most importantly, they provide a quantitative description of the tumour-induced mechanical modifications in the brain ECM, thus being of potential help in the search for novel ECM targets for brain tumours and especially for GBM that, despite years of intense research, has still very limited therapeutic options.