Glioblastoma is the most common and malign form of brain cancer that is highly resistant to therapy and particularly hard to cure since the blood-barrier is not very permeable to drugs. Moreover, a surgery is always highly risky. Thus, there is a real need to develop technique enabling accurate identification of potentially tumor cells at an early stage. It is getting well established that cancer cells are usually softer than their normal homologues and Atomic Force Microscopy (AFM) has proven itself over the last decade to be a tool of choice to characterize cells mechanical properties. Among the various AFM techniques, Force Spectroscopy (FS), especially Force Volume (FV) is the most commonly used. In the present study, AFM has been used to successfully characterize malignant and modified less malignant forms of glioblastoma U-251MG isogenic cells, using FV and Peak Force Tapping (PFT), a newly released AFM mode. Although both modes are quantitative and easy to use, PFT appears as the most relevant. Benefits and drawbacks of both techniques are discussed.