Purpose <p>The earliest known case of cemento-osseous dysplasia could be detected in a Bronze Age skeleton, dating back 4500 years ago in the region of the North Caucasus. Although the soft tissue was missing, sufficient diagnosis could be achieved by using different methods that prove the existence of fibro-osseous processes already in prehistory. Skeletal remains provide a direct view of such changes which cannot be obtained from a living patient without compromising.</p> Methods <p>A skeleton of a 30-40-year-old female individual from the burial mound of Budyonnovsk 10 (including 19 individuals) in Southern Russia was investigated using macroscopic, radiographic, and microscopic methods.</p> Results <p>In the mandible, destruction of the labial wall of the alveoli 32 and 31 is already visible macroscopically. At the base of the lesion, the original bone is replaced by fine porous bone including small dense particles: plain radiography and computed tomography evidence localized processes to the periapical areas of all lower incisors. The lesions are mainly radiolucent, only the particles in alveolus 32 have a radiopaque appearance. Microscopy shows woven bone as filling of the lesions and additional hypocellular materials in alveolus 32, which can best be explained as cementum-like structures.</p> Conclusions <p>The lesion´s location in the periapical areas of the lower incisors, the woven bone, and cementum-like structures fit the diagnosis of periapical cemento-osseous dysplasia. The presence of a second individual with focal cemento-osseous dysplasia in this burial mound is an interesting co-occurrence that requires further genetic analysis.</p> Limitations <p>The diagnosis is solely based on the skeletal remains, soft tissue components are missing.</p> Suggestions for Further Research <p>Genetic analyses are planned to detect the underlying mutation for the two individuals.</p>