p62/SQSTM1/Sequestosome‐1 is an autophagic protein of fundamental importance in cellular metabolism and tumor proliferatio. Moreover, autophagy may influence the development and resistance to therapy of numerous types of human cancer. In the present pilot study, the immunohistochemical expression of p62 was analyzed in a cohort of primary and recurrent glioblastomas IDH-wt, in order to verify the concordance or discordance between theprimary and recurrent tumors and to correlate this expression to genetic and clinic-pathological parameters. The results revealed p62 expression in the nucleus and cytoplasm of neoplastic elements in 45% of primary and 55% of recurrent cases of GBM. A discordant p62 immunoreactivity was detected in 35% of cases. Statistically, p62 expression and MGMT status exhibited a significant prognostic value by univariate analysis, whereas only MGMT promoter methylation status emerged as an independent prognostic factor by multivariate analysis. Finally, the most favorable prognosis was documented when the same GBM case was positively concordant for both p62 expression and MGMT methylated status. Since little data are available regarding the association between p62 expression and MGMT in GBM, further investigations may be required to determine if new targeted therapies may be addressed against autophagy‐related proteins, such as p62.