Plasmacytoma and multiple myeloma represent neoplastic proliferations originating from plasma cells that frequently affect the spine, pelvis, skull, ribs, vertebrae and long bones. Gnathic bones are involved in up to 30% of the cases. Males are more affected and patients are usually in their sixth to seventh decades of life. Plasmacytoma manifests as a solitary lesion in the bone (solitary plasmacytoma of bone) or in an extramedullary site (extramedullary plasmacytoma), whereas multiple myeloma is characterized by clinical, radiological and laboratory manifestations that include multiple bone lesions, anemia, hypocalcemia, renal impairment, monoclonal protein (M-protein) deposition and Bence-Jones proteinuria. In the jaws, plasmacytoma and multiple myeloma present as radiolucent, ill-defined images, more often in the posterior region of the mandible. The lesions may be painful or asymptomatic, and present as non-ulcerated growths or may reveal extensive regions of tissue necrosis and ulceration. Histologically, neoplastic plasma cells exhibit different grades of pleomorphism and express plasmacytic markers like CD38, CD138, EMA and MUM1. Amyloid deposits can be found. Plasmacytoma is often treated by surgery, radiation and/or systemic therapy, while multiple myeloma is considered an incurable disease, despite improvements in treatment modalities that have significantly increased survival rates.