Activating FGFR3 germline mutations cause skeletal dysplasia and craniosynostosis syndromes. Somatic FGFR3 mutations have been identified in several cancer entities such as urothelial carcinoma and multiple myeloma. Recently, the same FGFR3 mutations known from skeletal dysplasia syndromes and urothelial carcinoma have been shown to cause benign human skin tumors such as seborrheic keratoses and epidermal nevi. The underlying mechanisms for the somatic FGFR3 mutations in the epidermis are unknown so far, as well as details of the involved signaling pathways in the mutant keratinocytes leading to the formation of acanthotic skin tumors. Herein we discuss potential mechanisms and functional consequences of activating FGFR3 mutations in human skin. Further studies are required to provide insights in the pathogenesis of benign skin tumors caused by FGFR3 mutations. These studies will add to new non-invasive therapeutical strategies for benign acanthotic skin tumors in dermatology.