Background: Breast cancer is the most frequently diagnosed cancer and the most common cause of cancer deaths in women worldwide. Ki67 is a biomarker that reflects cell proliferation. Despite a clear understanding of the structure and properties of this protein, its functional role remains elusive. Gene expression alteration confers the potential for invasive growth in the preinvasive stages of breast cancer. Altered expression of the tumor suppressor gene p53 is frequently seen in carcinomas of the breast and correlates with poor prognosis. This study aims to investigate Ki67 and p53 expressions in benign, preinvasive and invasive breast lesions and to correlate their expressions with the clinico-pathological parameters. Materials and Methods: This study included 74 specimens of breast lesions. Ki67 and p53 immunostaining expression was detected using avidin-biotin peroxidase method. Results: Ki67 and p53 increased progressively along the continuum of neoplastic changes from normal breast epithelium to invasive ductal carcinomas; IDC (P<0.000 & P<0.01 respectively). There was significant positive correlation between Ki67-labeling index (LI) and either tumor grade or lymph node metastasis in IDC (P<0.03 & P<0.02 respectively). P53 expression increased with increasing grade of both ductal carcinoma in situ (DCIS) and IDC (P<0.01 & P<0.002 respectively). There was significant correlation between p53 and tumor size, lymphovascular invasion, and lymphocytic infiltration (P<0.05, P<0.02, P<0.03 respectively). There was positive correlation between Ki67 and p53 in DCIS (r= 0.845, P<0.001) and IDC (r=0.697, P<0.02) of the breast. Conclusion: Ki67 and p53 increased progressively along the continuum of neoplastic changes from normal breast epithelium to DCIS and IDC. Ki67 and p53 were increased with poor prognostic parameters; tumor size, tumor grade, lymphovascular invasion, lymphocytic infiltration, and lymph node metastasis.