Background and Objective: Histological grading has prognostic and therapeutic implications in meningioma. However, histological criteria are sometimes not fulfilled to predict the biological behavior of meningiomas. P63 gene is a novel P53 family member, known as tumor suppressor factor, with multiple isoforms and shows high expression in many normal and neoplastic human tissues. In this study, we investigated expression of P63 in different histological grades of meningiomas. Material and Methods: For this purpose, we studied and analyzed the immunohistochemical expression of P63 by a monoclonal antibody (clone 4A4) that recognizes all P63 isoforms in 52 cases of meningioma including WHO grade I (42 cases), grade II (7 cases) and grade III (3 cases). Correlation between histological grade and parameters like cell nuclear immunoreactivity to P63 antibody, age, gender and site of meningioma was analyzed by parametric and non-parametric statistical tests. Results: Among 52 patients analyzed, there were 35 females (67.3 %) and 17 males (32.7%) between 13 and 75 years old. Histological grading revealed 42 cases (80.8%) as WHO grade I, 7 (13.5%) as grade II and 3 (5.8%) cases were grade III. Expression of P63 protein was found in 83.2% of cases with grade I but in grade II and III, all of the cases were immunoreactive, so as in grade III, 100% of cases were with higher percent of nuclear reactivity in our study. Correlation between histological grade and nuclear immunoreactivity was highly significant (p=0.001). Conclusion: We conclude that the immunohistochemical staining of P63 will be valuable in discrimination of different grades of meningiomas.