Glioblastoma is the most frequent and aggressive primary brain tumor in adults. Recently, a growing number of studies have shown that denaturation profile of plasma samples obtained by differential scanning calorimetry (DSC) can represent a signature of a disease. In this study, we analyzed for the first time the DSC denaturation profiles of the plasma from patients with recurrent glioblastoma (n=17). Comparison to the one of healthy individuals (n=10) and to already described profiles in others cancer showed clear differences suggesting that this DSC profile may constitute a signature of glioblastoma. Parameters extracted from these profiles were used for cluster analysis which revealed the existence of glioblastoma profile subgroups which correlated with prognostic factors. Moreover, we showed that the presence of circulating bevacizumab and carmustine did not alter this calorimetric signature of the disease, indicating that an evolution of the profile could be followed without being masked by ongoing systemic treatment. Thus, our results constitute a very promising proof of principle that a specific calorimetric profile could be detected in the plasma of glioblastoma patients. Moreover, we believe that our findings point to a potential easy-to-use non-invasive monitoring tool for glioblastoma patients.