The reasons why a specific subset of glioblastoma (GBM) patients survive longer than others is still unclear. This study analyzed a cohort of long-term and very-long-term GBM survivors to determine which genetic alterations or patient's characteristics influence survival time.We retrospectively reviewed a cohort of GBM patients treated at our institution over the last 20 years, stratifying patients in three groups: those with a survival time ≥ 36 months and 120 months (LTS), ≥120 months (VLTS), and 36 months, respectively. Clinical (age, sex, focality, resection degree, Karnofsky performance status), and immunohistochemical and molecular data (Ki-67 expression and multiple genes alterations) were collected. We then utilized principal component analysis, logistic regression, and Cox proportional hazard models to identify those variables associated with survival.Younger age at presentation (HR = 0.36, 95% CI 0.21-0.67, p = .001), and MGMT promoter [(MGMTp), methylated, HR = 0.57, CI 0.34-0.96, p = .034) were associated with higher odds of VLTS survival. The multivariate analysis showed how the combination of younger age (50 years), Ki-67 10%, and the coexistence of TERTp not mutated, MGMTp methylated, and IDH1/2 mutated in the same patient are also associated with higher odds of survival (HR = 0.10, CI 0.01-0.74, p = .025).We confirmed younger age at presentation and MGMTp methylation as the only independent factors associated with VLTS. The exceptional survival of our VLTS patients is probably associated with different, still understudied, gene mutations, or with the coexistence of multiple factors.