Primary non-Hodgkin's lymphoma of bone (PLB) constitutes approximately 5% of all extranodal non-Hodgkin's lymphoma (NHL) and 7% of primary bone tumors. The peak incidence for PLB is in the fifth decade, with a slight preponderance of males over females. The presenting symptoms usually consist of localized bone pain and occasionally a palpable mass. Most patients with PLB have B-cell tumors with a diffuse mixed-cell or diffuse large cell histology. While most patients present with early-stage disease, it is not clear whether such patients benefit from combined-modality therapy (CMT) consisting of radiation therapy (RT) and chemotherapy (CT) compared with either RT or CT alone. However, there is strong evidence that CMT is beneficial in the treatment of localized NHL, and these results might be applicable to the therapy for PLB. Nevertheless, only a phase III randomized, controlled clinical trial will determine whether CMT is superior to either CT or RT alone.