The surgical biopsy from astrocytomas is usually obtained from enhanced lesion but sometimes may include fragments of apparently normal brain tissue /peritumoral areas. We hypothesize that the evaluation of these fragments for presence of cancer stem cells may have prognostic and /or diagnostic implication. This work has been planned to 1) verify nestin and hypoxia inducible factor-1α location in apparently normal brain tissue/peritumoral areas and its relation to the presence of neoplastic cells in these fragments and 2) analyze  the correlation between nestin and hypoxia inducible factor-1 α expression in apparently normal brain tissue/peritumoral areas adjacent to different grades of astrocytomas.  Material and Methods: Paraffin-embedded sections of selected thirty  specimens of astrocytomas contain apparently normal brain tissue/peritumoral areas  (12 diffuse astrocytomas, 6 anaplastic astrocytomas and 12 glioblastoma multiforme) were stained with nestin and hypoxia inducible factor-1α using standard immunohistochemical approaches. The immunoreactivity for nestin and Hypoxia-inducible factor -1 α was evaluated.  Results: Compared to nearby astrocytomas, nestin immunoreactivity was scarcely expressed in apparently normal brain tissue/peritumoral tissue. There was  statistically  significant (P =0.03) gradual increase of mean percentage of nestin positive cells that present in these fragments with increasing grade of the adjacent astrocytomas from diffuse astrocytoma to anaplastic astrocytoma to glioblastoma multiforme (27.1± 4, 38.3±3 and 47.5±5.9, respectively). There was statistically insignificant (P < 0.1) gradual increase of mean percentage of hypoxia inducible factor-1α positive neoplastic cells that infiltrate peritumoral areas with increasing grade of the adjacent astrocytomas. There was statistically significant gradual increase of counting of microvessels that showed positivity for nestin and hypoxia inducible factor-1α expression with increasing grade of the adjacent astrocytomas (P=0.008, P=0.01, respectively). Conclusion: Nestin and hypoxia inducible factor-1α was expressed in apparently normal brain tissue/peritumoral tissue adjacent to astrocytomas. Positivity for nestin in apparently normal fragments may indicate premalignant changes or nearby tumor when a biopsy contain only apparently normal brain tissue. Evaluation of nestin expression in peritumoral areas may have prognostic value as it may be an indicator for rapid recurrence and resistance of treatment.