Background Basal cell carcinoma (BCC) is the most common cutaneous malignancy and may show various differentiations. The possible pluripotent stem cell lineage of BCCs, whose origins are controversial today, is thought to be the main reason for the different morphologies. The aim of the study is to evaluate the expression of some neuroendocrine and smooth muscle markers of differentiation in BCCs and investigate the relationship between histopathologic subtypes and recurrence. Methods A total of 128 cases diagnosed as BCC in our center were included. Immunohistochemical studies of CD56, synaptophysin, chromogranin-A, smooth muscle actin (SMA), desmin, caldesmon, and Ki67 were applied. Results CD56, chromogranin-A, and synaptophysin immunoreactivity were detected in 77.3%, 13.3%, and 0.8% of the cases, respectively. 78.1% showed SMA positivity while no tumor expressed desmin or caldesmon. A correlation between histopathologic recurrence risk groups and CD56 expression was found (p < 0.05). Conclusions CD56 and SMA immunoreactivity is present in the majority of BCCs. However, the available findings do not support neuroendocrine or smooth muscle differentiation. CD56 antigen can be used for prognostic purposes in detecting high recurrence risk tumors. After the investigation of the expression rates of these two antigens in different cutaneous tumors, it may be appropriate to use them for diagnostic purposes in BCCs.