Palmoplantar keratoderma of Sybert (PPK of Sybert) or Sybert’s keratoderma was first documented by Virginia Sybert in 1988. Due to the high degree of similarity, it was previously considered to be Greither’s keratoderma, an established entity at that time. Currently, clinical and ultrastructural studies distinguish between the two disorders. Sybert’s keratoderma is an extremely rare type of keratoderma with an autosomal dominant mode of inheritance caused by mutations to the keratin 1 gene along with severe bilateral involvement of the palms and soles with a tendency for proximal extension and natal cleft in the absence of systemic manifestation. To the best of our knowledge, there are less than 20 cases of PPK of Sybert reported in the literature. Here we discuss an extremely rare familial PPK of Sybert that has affected 4 family members. The cases presented with symmetrical, severe involvement of their palms, soles, and knees with the development of pseudoainhum and autoamputation of the fingers and/or toes.