Cluster of differentiation 44 (CD44) expression in breast carcinoma is associated with basal-like epithelial markers in tumor cells, advanced tumor stage, and metaplastic variants. Since CD44 is a recently identified marker, further research is necessary to understand its immunoexpression and its relationship with hormone receptor status and other prognostic factors that influence patient management and therapy. This study was conducted to assess the expression of CD44 in breast cancer tissue. A cross-sectional investigation was conducted in our hospital on 60 mastectomy specimens received in the histopathology section of the Department of Pathology. The patient's age, tumor size, histological type, histological grade, and lymph node status were recorded. Immunohistochemical staining for estrogen receptor (ER), progesterone receptor (PR ), human epidermal growth factor receptor 2/neu (HER2/neu), and CD44 markers was performed, and expression of CD44 was correlated with these clinicopathological and prognostic parameters. The results were subjected to statistical analysis. CD44 expression was detected in 51 of the 60 cases (85%). A statistically significant correlation was found between the expression of CD44 with patients' age, size of tumor, histological grade, and HER2/neu hormonal marker. No statistically significant relationship was observed between other factors, such as lymph node status and the expression of ER and PR. The expression of CD44 showed a strong correlation with known poor prognostic indicators, such as HER2/neu status and histological grade. Therefore, CD44 expression indicates an aggressive tumor biology and can serve as an independent marker for prognosis and therapy.