We report a case of a 63-year-old man with a history of numerous basal cell carcinomas (BCCs) on vismodegib who developed a pink subcutaneous nodule that was thought to be either a BCC or an epidermal inclusion cyst. Sections displayed a dome-shaped lesion composed of large dermal nodules of epithelioid cells with variable cytology. Some of the dermal nodules demonstrated squamatization of the epithelioid cells while others had a predominantly basaloid phenotype. Central necrosis was present in the majority of the large dermal nodules, but the lesion did not stain with CK7 or CK20, helping to rule out internal metastases. The epithelial nodules stained strongly with pancytokeratin (AE1/AE3), p40, and stained lightly with BCL-2, supporting the diagnosis of BCC. However, Ber-EP4 being negative and the presence of significant squamatization suggest vismodegib can alter both the histological and immunophenotype of BCCs. This phenomenon has rarely been reported in literature.