An estimated 6-yr-old female leopard gecko (Eublepharis macularius) presented with a raised spherical mass on the head. Grossly, the skin overlying the mass was smooth, with a focal area of ulceration. Histologically, the dermis was expanded by a well-demarcated, poorly cellular single expansile cyst. The cyst was lined by stratified squamous epithelium and was filled with an accumulation of tightly packed lamellar keratin with regular folding, resembling keratinization of the epidermis. Neither cellular nor nuclear atypia was observed, and there were no mitotic figures in the lining epithelium. The histopathological findings were consistent with an epidermal cyst. To the best of the authors' knowledge, an epidermal cyst in the dermis of the head has not been documented previously in a captive leopard gecko.