Buschke-Fisher-Brauer keratoderma is a rare hereditary autosomal dominant disease of incomplete penetrance. Important differential diagnoses include other palmoplantar keratinization disorders, acquired or hereditary, which is done based on the histopathological findings. This diagnosis alerts especially about the possibility of associated neoplasms. Treatment involves topical keratolytic agents, usually with little efficacy, or with long-term systemic retinoids with follow-up of exuberant collateral effects.