Background Breast cancer is the most common cause of cancer death among women worldwide. Adhesion molecule EpCAM is an important player in carcinogenesis; however, its exact biological role is not clear. Tumor suppressor gene p53 maintains genomic stability. In malignant cells, its function can be compromised by various mechanisms such as mutations, alteration of p53 regulators, and alteration of p53 target genes. This study aimed to find the relationship between epithelial cell adhesion molecule (EpCAM) and p53 expressions on one hand and clinicopathological factors of prognostic importance in breast cancer on the other hand and find any correlations between EpCAM and p53 markers. Materials and methods Immunohistochemical staining with EpCAM and p53 was studied on 42 cases of infiltrating duct carcinoma. Results A significant association was found between EpCAM and tumor size (P=0.049), tumor grade (P=0.005), lymph node status (P=0.043), pathological tumor stage; pathological tumor stage (P=0.027), and lymphovascular invasion (P=0.048). However, EpCAM was negatively associated with estrogen receptor (P=0.007), progesterone receptor (P=0.031), and human epidermal growth factor receptor 2/neu (P=0.025) expressions. Expression of p53 was positively associated with tumor size (P=0.025), tumor grade (P=0.002), lymph node status (P=0.05), pathological tumor stage (P=0.041), and lymphovascular invasion (P=0.043), while negatively associated with estrogen receptor (P=0.029), progesterone receptor (P=0.043), and human epidermal growth factor receptor 2/neu (P=0.039) expressions. A positive association was found between EpCAM and p53 expressions and triple-negative breast cancer (P=0.007 and 0.029, respectively). There was a positive association between EpCAM and p53 (P=0.007). Conclusion EpCAM and p53 expressions are good markers of predicting poorer outcomes in breast cancer patients. There is a positive association suggesting a combined prognostic value in breast cancer and it may confirm the binding of p53 with the EpCAM gene to regulate its function.