Background and Objective: Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are two common tumors of the skin. In some cases, distinction between BCC and SCC can be difficult. This study aimed to clarify this uncertainty through immunohistochemical analysis. In this respect, epithelial membrane antigen (EMA) and Ber-Ep4 are the two immunohistochemical markers on which we focus in differentiating skin BCC from SCC. Materials and Methods: Archived paraffin-embedded tissue samples of BCC (n = 40) and SCC (n=40) were stained immunohistochemically using Ber-Ep4 and EMA antibodies. Results: It was found out that 37 (92.5%) out of the BCC samples stained positive for Ber-Ep4 and 2.5% of SCC samples showed positive staining. The majority of SCC group (37 out of 40) expressed EMA, while 5% of BCC samples showed positive staining. Conclusion: Distinction of BCC and SCC of the skin can be readily achieved through Ber-Ep4 and EMA immunohistochemical markers. Regarding potential false positive and negative results through immunostaining techniques, we may recommend the use of these two antibodies together.