We present two cases of extramedullary plasmacytoma presenting as a mediastinal mass and preceding the onset of full-blown multiple myeloma. The patients are a 62-year-old woman who presented with progressive dyspnea and left-sided chest pain and a 59-year-old asymptomatic man. In both patients, radiographic studies revealed a posterior and anterior mediastinal mass, respectively. Surgical resection of the tumor was performed in the two cases. The tumors were characterized by a well-circumscribed proliferation of plasma cells surrounded by residual lymph nodal tissue. Immunohistochemical studies on paraffin sections demonstrated lambda light chain restriction. Follow-up in our patients revealed that both of them developed multiple myeloma after 6 months and 2 years, respectively. One patient received treatment with melphalan and prednisone and is currently alive and well without evidence of disease, 2 years after diagnosis. The second patient died 4 years after resection of his tumor with evidence of disease in lumbar spine, skull, and lungs. Extramedullary plasmacytoma presenting as a mediastinal mass may precede the onset of full-blown multiple myeloma; therefore, institution of early systemic therapy in these patients may be of value in preventing further progression of the disease.