Dermatofibroma is a common skin benign cutaneous tumor with many variants based on alterations in the morphology and composition of its diverse elements. The cause of dermatofibroma is unknown, it was his- torically attributed to being a reactive response to some traumatic lesion to the skin which is associated with itching and pain. This tumor usually appears on the limbs, especially the end extremities, in young adults. In the present study, a middle-aged Persian leopard was accidentally killed because of a car incident in the Golestan National Park, Iran. Following necropsy, skin mass on the right toe was observed and after sam- pling was transferred to the laboratory. After routine histopathological and immunohistochemical processes, Dermatofibroma was diagnosed microscopically with non-capsulated, circumscribed, hypocellular dermal nodule in a spiral pattern. According to the results of this study immunohistochemical staining revealed positivity for CD34. There is limited information about the Dermatofibroma in leopards. To our knowledge, this is the first report of Dermatofibroma in the Persian leopard.