While keratoacanthomas (KAs) and squamous cell carcinomas (SCCs) have been reported in response to a number of systemic drugs such as vemurafenib, sorafenib, or voriconazole,1-3 their association with Smoothened inhibitors has not been previously noted. Herein, we report 2 cases of new KAs developing within 2 months of starting vismodegib therapy in individuals with no history of KAs or SCCs.