Alteration of the P53 tumor suppressor gene is implicated in tumorigenesis and in progression of a wide variety of human cancers, including gliomas. Accumulation of P53 protein is used as indicator of alteration in P53 gene. Less is known about P53 expression in reactive non-neoplastic lesions (gliosis). This work is done to verify the presence of P53 in astrocytomas through immunohistochemistry as well as correlating its expression with clinicopathological parameters and to detect its role in differentiating gliosis from low grade astrocytomas. Ninety-one astrocytomas and 24 cases of reactive gliosis were retrospectively collected from Pathology Department in Assiut University Hospital and private laboratories. Astrocytomas were classified and graded according to WHO classification (2000) using H&E stained sections from formalin fixed paraffin embedded blocks. P53 was immunohistochemically evaluated in selected 46 cases of astrocytomas and 12 cases reactive gliosis. Glioblastoma multiforme (WHO grade IV) was the predominant grade of astrocytomas. The mean age of patients with astrocytomas showed upergulation with grade. There was male sex predilection in all grades of astrocytomas. P53 protein was detected in 58.7% of astrocytomas including all grades. The immunoreactivity score showed gradual upergulation with increasing grade. There was positive insignificant correlation between P53 expression and age, cellularity & mitosis and positive significant correlation between its expression and pleomorphism, microvascular proliferation & necrosis. All cases of gliosis except one showed negative P53 immunoreactivity. In conclusion: P53 protein alteration is an early event in tumorigenesis and progression of astrocytomas and is a useful diagnostic tool in diagnosis of high grade gliomas. P53 provides just one more procedure in differentiation of gliosis from low grade astrocytomas.