Although basal cell carcinomas (BCC) show typical histomorphologic features, they sometimes remain difficult in distinction from benign adnexal skin tumors of follicular origin like trichoepithelioma (TE) or trichoblastoma (TB). Consequently, an immunohistochemical marker panel separating described entities would be helpful in clinical routine. Thus, we stained 22 skin lesions (BCC, TE, and TB) against β-catenin, CK20, E-cadherin, p40, and p63. The staining pattern was described and quantified using an immunohistochemical score. Although p40 and p63 revealed a strong staining intensity of all skin lesions without distinction between BCC and benign lesions (P=1.000), established Merkel cell marker CK20 illustrated a loss of staining in BCC compared with TE and TB (P=0.007). In contrast, BCC exhibited an increased expression of E-cadherin in relation to TE and TB (P=0.009). Single application of CK20 or E-cadherin could predict diagnosis of BCC in 81.8% or 72.7%, respectively. Combining consecutive staining of E-cadherin and CK20 could even enhance specificity toward diagnosis of TE or TB. Hence, findings of our study imply that sequential staining of CK20 and E-cadherin prevents false-positive classification of BCC. Furthermore, our study demonstrated that p40 exhibits the same staining pattern in BCC, TE, and TB. Therefore, p40 might replace p63 equivalently establishing diagnosis of primary adnexal neoplasms of the skin in the form of BCC as well as benign adnexal tumors. As a result, the depicted immunohistochemical marker panel may be applied for adnexal skin neoplasms as a diagnostic adjunct especially in surgically challenging body regions.