MRONJ is a well-known side effect of various medications, such as antiresorptive drugs, anti-angiogenic agents, immunomodulators and immunosuppressants. MRONJ related to immunotherapy is rarely described, with only one case related to ipilimumab. The interaction between the immune system and osteoclast lineage cells is well known. T cells release factors and cytokines that control osteoclastogenesis, and osteoclasts produce factors with an action on T cells. We attempted to explain how immunotherapy could cause MRONJ through the case report of a young patient with metastatic melanoma who developed maxilla MRONJ after pembrolizumab and epacadostat treatment.