P75 neurotrophin receptor (p75) is a transmembrane protein in the tumor necrosis receptor superfamily useful for the diagnosis of desmoplastic melanomas, desmoplastic trichoepitheliomas, and more recently used for detecting perineural invasion in oral and esophageal squamous cell carcinomas (SCCs). P75 staining in cutaneous SCCs is more controversial with initial staining reported as negative but more recent reports indicating that it may be a useful immunohistochemical marker of perineural invasion. A poorly differentiated pleomorphic epithelioid cell proliferation, which had strong p75 staining in the periphery of epithelioid cell nests, is being reported. Both low and high molecular weight keratins were positive and SOX10, S100, and HMB-45 staining were negative, consistent with a poorly differentiated SCC. To our knowledge, this pattern has not yet been reported and most likely reflects reiteration of the basal layer epithelium, which normally stains positively for p75. Reports of p75 staining in cutaneous SCCs are still limited, and a larger scale study may prove useful in determining its role as a marker for perineural invasion.