We herein describe a rare case of multiple myeloma with an aggressive clinical course and the unusual manifestation of multiple organ involvement by plasma cells. A 58-year-old man noted difficulty in walking due to progressive swelling of his left lower limb. CT scan revealed a huge mass in the inguinal region in addition to masses located on the head, and in the aero-digestive tract and spinal canal. The pathological diagnosis of plasmacytoma was made on biopsied specimens of these masses, while plasma cells did not increase (5.8%) in aspirated bone marrow obtained at the same time. Serum IgG level was 6,387 mg/dl and immunoelectrophoresis demonstrated monoclonal IgG-kappa in the serum. Chemotherapy with vincristine, adriamycin, dexamethasone, subsequent high-dose cyclophosphamide, and irradiation involving both thoracic vertebral canal and inguinal regions resulted in improvement of initial symptoms. However, the patient relapsed soon after; new lesions developed in various parts of the body, including the left thigh and body trunk. Salvage therapy including bortezomib was no longer effective, and he eventually died 10 months after the initial diagnosis. Autopsy revealed the diffuse involvement of plasma cells of multiple organs, including the liver, spleen, abdominal lymph node, and bone marrow in addition to the left leg.