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Background: The cyclooxygenase-2 (COX-2) enzyme is overexpressed in different types of tumors and is known to be associated with malignant behavior of tumors. We determined the association of COX-2 expression and different grades of human meningioma. Materials and Methods: This retrospective study was conducted on specimens obtained from adult patients with meningioma. Meningioma was classified according to the WHO 2007 classification protocol (I, II, and III). COX-2 expression intensity was scored based on the percentage of immunopositive cells as 0: 0-10%; +1: >10% and a part of the cell membrane; +2: >10% and complete cell membrane; and +3: >30% and complete cell membrane. Scores of +2 or +3 were considered as COX-2 positive. Results: Ninety meningioma cases (mean age = 53.0 ± 13.2 years, 71.1% female) were studied. COX-2 was positive in 25% (17/68), 68.4% (13/19), and 100% (3/3) of cases with tumor grade I, II, and III, respectively (P < 0.001). There was a significant correlation between tumor grade and COX-2 expression score (Spearman′s correlation coefficient = 0.422, P < 0.001). Conclusions: There is a strong association between COX-2 expression and tumoral grade in meningioma with more aggressive tumors expressing COX-2 with more intensity. Prospective studies examining the association of COX-2 expression with tumor recurrence and interventional studies examining the role of COX-2 inhibitors anticancer therapy of meningioma are warranted.