The stratum corneum (SC), the top layer of the epidermis, is the functional site of the skin barrier and serves to maintain hydration of the body by preventing water loss and thwarting the entrance of pathogens. The naked mole rat (NMR) (Heterocephalus glaber) is a rodent that resides in hypoxic underground tunnels in arid Africa. NMRs are not only hairless; their skin is devoid of glands and pain sensation. To understand how the skin barrier of the NMR is uniquely adapted to this environment, skin samples from the dorsum and ventral abdomen in one adult and one neonate were examined by transmission electron microscopy using both reduced osmium tetroxide to assess overall structure and ruthenium tetroxide post-fixation to assess lipid organization. These findings were compared with that of hairless mice-a well-defined model for skin barrier studies. The plasticity of the skin was evaluated on 10 NMRs from a colony at the Philadelphia Zoo in humid and dry conditions by measuring cutaneous hydration, transepidermal water loss (TEWL), and pH. The epidermal ultrastructure of the NMR differed from hairless mice by having the following features: decreased content of lamellar bodies (LBs), higher LB pleomorphism, periodic presence of abnormal lipid bilayers, and an unusually thick SC. The NMRs developed significant TEWL and a trend toward decreased hydration when subjected to dry conditions. While these features illustrate an imperfect skin barrier in terrestrial mammals, they likely represent adaptations of the poikilothermic NMRs to their unique natural fossorial climate. Prolonged exposure to decreased humidity could possibly lead to adverse health effects in this species.