Pigmentation anomalies may occur due to genetic or environmental factors and can affect restricted parts of the body or the entire surface. Eleutherodactylus zeus is frog endemic to western Cuba where it is adapted to life in caves, rock crevices, and other sheltered sites in limestone landscapes associated with forest habitats. We observed 43 frogs in Santo Tomás cave, in Viñales National Park, of which 26 % showed depigmented blotches, typical of piebaldism, along their bodies. No unusual behaviour was detected in any of these frogs. This is the first reported case of piebaldism in frogs of the West Indies and consequently of Cuba. Records of piebaldism in amphibians are very scarce in the literature, not necessarily as a consequence of its rarity in nature but possibly due to inconsistencies in the classification of pigmentation abnormalities.