BACKGROUND AND AIMS: The cell surface glycoprotein CD44 plays an important role in mediating cell to cell and cell to matrix interaction, hence promoting the maintenance of tissue integrity and inhibiting tumour metastasis. The present study is aimed to evaluate the expression of CD44 by immunohistochemistry in prostatic core biopsies and transurethral resection of prostate (TURP) specimens in prostatic lesions. METHODS: A total of 63 prostatic samples were enrolled in the study which included cases of benign prostatic hyperplasia, prostatic intraepithelial neoplasia and prostatic adenocarcinoma. Immunohistochemical expression of CD44 was studied to assess its association with histopathological findings and clinical data in the aforementioned samples. RESULTS: CD44 expression was strongly expressed in inflammatory and non-neoplastic cells as compared to neoplastic cells. Within the later, intensity of CD44 expression was stronger in well-differentiated than in poorly differentiated tumours. Loss of CD44 expression was associated with greater tumour aggressiveness. The positive expression of CD44 expression on immunohistochemistry was strongly associated with lower S. PSA levels, Gleasons scores & grades. Consequently, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of negative CD44 expression for the diagnosis of prostatic adenocarcinoma were 93.3%,79.3%,82.4%,92% and 86.4% respectively. CONCLUSION: There is a great requirement for markers that distinguish slowly progressive from rapidly progressive prostate cancers in paraffin-embedded tissues. CD44 promotes the maintenance of tissue integrity and its expression in prostate cancer is associated with reduced tumour aggressiveness. The up-regulation of the expression of CD44 by certain microRNAs can be utilized as a novel therapeutic agent against prostatic adenocarcinoma.