Phosphorylated cyclic-AMP responsive element binding protein (p-CREB) is a transcription factor that is involved in gliomagenesis. For this reason, it was recently proposed as a potential therapeutic target in gliomas; however, gliomas comprise tumors with different biomolecular profile, clinical behavior, and response to chemotherapy. In the present study, we aimed to investigate whether p-CREB expression varies in the 2 main types of gliomas, astrocytomas and oligodendrogliomas. Thus, we analyzed the expression of p-CREB in a series of astrocytomas and oligodendrogliomas of different histologic grades by immunohistochemistry and Western blot analysis. p53 overexpression and the Ki-67 labeling index were also assessed in all the tumors. p-CREB immunohistochemical expression was present in 100% of the astrocytic tumors, but in only 46% of oligodendrogliomas (P = .0033 for grade II; P = .0041 for grade III tumors). Absence of p-CREB immunohistochemical expression was significantly associated with 1p/19q codeletion (P < .0001) and identified 1p/19q codeleted tumors, with 70% sensitivity and 100% specificity (area under the curve = 0.85; P < .0001). In addition, p-CREB expression correlated with higher Ki-67 labeling index (P = .049) and p53 overexpression (P < .0001) as well as with the histologic grade of astrocytomas (P = .044). Immunohistochemical results were further confirmed by Western blot analysis. Our findings demonstrate that astrocytomas and oligodendrogliomas are characterized by distinctive patterns of p-CREB expression. These distinct expression patterns might provide insight into the mechanism of tumorigenesis of glial tumors and represent a useful tool for the differential diagnosis of astrocytoma and oligodendroglioma., (Copyright © 2015 Elsevier Inc. All rights reserved.)