Hereditary punctate palmoplantar keratoderma or Buschke-Fisher-Brauer disease is a rare form of keratoderma that follows a pattern of autosomal dominant inheritance with variable penetrance. The age of onset is usually between 12 and 30 years of age. Clinically, it is characterized by the gradual appearance of multiple punctate hyperkeratotic papules, irregularly distributed on the palms and soles, as well as by its possible association with several diseases, primarily with malignant processes. We present the case of a 43-year-old male patient with this disease, with no other associated symptoms, who had a first-degree relative who was affected and died of colon cancer. We also discuss the differential diagnosis with other nosologic entities.