The best treatment of primary lymphoma of bone (PLB) remains undefined. We reviewed 15 patients with monostotic PLB and 8 with polyostotic PLB. Twenty of the patients were suitable for analysis. All patients but 1 received adriamycin-containing chemotherapy in association with radiation therapy. Radiotherapy for monostotic cases consisted of 40 Gy to long bones, followed by a boost to 45 Gy to bulky lesions or 40-45 Gy to whole flat bones. In cases of polyostotic PLB, bulky sites, fractured lesions, or sites with a high risk of fracture were irradiated with a median dose of 38 Gy. All patients with monostotic disease achieved complete remission (CR): 10 patients were alive and relapse-free at the time of this writing, 1 other patient was alive following a relapse, and 1 patient died while relapse-free. The survival rate for the patients in the study at the time of this writing was 92% at 50 months. Four patients with polyostotic disease achieved CR. Three of them had only two adjacent sites of disease and were treated as cases of monostotic PLB. Two of these 3 patients are alive and relapse-free. Four patients with polyostotic disease achieved PR, relapsed rapidly, and died of progressive disease. The relapse site was invariably the skeleton. The survival rate for patients with polyostotic PLB at the time of writing was 25% at 40 months. No severe late treatment-related toxicity was observed. The treatment of patients with monostotic PLB with adriamycin-containing chemotherapy and whole-bone irradiation with 40 Gy, followed by a boost to 45 Gy to bulky sites, prevented local relapse and produced a more favorable outcome than the use of radiotherapy (RT) alone. Patients with multiple adjacent lesions that can be included within a single radiation field with acceptable toxicity should be treated as cases of monostotic PLB.