Naked mole-rats are highly valuable research models and popular exhibition animals at zoos worldwide. Here, we provide comprehensive descriptions of common postmortem findings of naked mole-rats from both research colonies and populations managed in zoological institutions. Included are brief reviews of their natural history and related physiologic adaptations, unique anatomical features, gross and histologic lesions of common as well as rarely reported disease processes, and discussions of possible pathogeneses with recommendations for future investigations to fill knowledge gaps. Based on postmortem data of several hundreds of naked mole-rats in managed care, it is clear that cancer is extremely rare and infectious disease is infrequently reported. However, despite relatively benign aging phenotypes in this species, several degenerative processes have been nevertheless observed in older populations of naked mole-rats. As such, some potential diet and husbandry-related issues are discussed in addition to the one of the most prominent causes of morbidity and mortality, conspecific aggression and traumas. From this review of lesions and disease, it is clear that pathology, including histopathology, is integral to better understanding mechanisms of healthy aging and cancer resistance of these extraordinary rodents.