Abstract: Objective :Primary central nervous system lymphoma (PCNSL) is a type of lymphomawhich originates in the central nervous system and does not spread to other systems. The incidence ofPCNSL is increasing, and its prognosis is poor. This study aims to investigate the diagnosis of PCNSLand to explore the most effective treatment for PCNSL in immunocompetent patients. Methods :Twen-ty-one cases (12 men and 9 women) with pathologically confirmed PCNSL were treated in our hospitalfrom June 1993 to June 2006. The clinical characteristics, the differential diagnosis and the treatmentswere reviewed retrospectively. SPSS 11.5 statistical analysis software was used to compare the twomethods of treatment: chemotherapy after radiotherapy and radiotherapy after chemotherapy. The sur-vival curves were calculated according to the Kaplan-Meier method and compared the Log-rank test. Results : The age of the patients ranged from 46 to 55 years old (median age=50). Multiple lesions werereported in 6 cases and single lesions in 15 cases. Computed tomography (CT) and magnetic resonanceimage (MRI) showed unique or multiple periventricular, uniformly enhancing lesions with mass effect,clear margins and moderate perifocal edema. All cases were B-cell lymphoma. No positive case of cere-brospinal fluid (CSF) was found upon cellular examination. Three cases received stereotactic brainbiopsy while others were given surgical treatment. Two cases received radiotherapy only after surgery;two cases received chemotherapy only after stereotactic brain biopsy while the remaining 17 cases re-ceived both radiotherapy and chemotherapy after stereotactic brain biopsy or resection. We divided the17 patients into two groups:Group 1 and 2. Group 1 was given chemotherapy after radiotherapy, whileGroup 2 was given radiotherapy after chemotherapy. Kaplan-Meier analysis showed that the mediansurvival time (MST) was 22.6 months and the 2-year survival rate was 44.5% across the whole group.Log-Rank test revealed that the survival time shows no statistical difference between Group 1 andGroup 2 (P=0.054 7). The MST of Group 1 and Group 2 were 36 months and 19 months and the 2-yearsurvival rates were 66.7% and 35.7%, respectively. Conclusion :PCNSL often occurs in middle-agedpatients, with intracranial hypertension as the main clinical manifestation. B-cell lymphoma is the mainpathological subtype. It is difficult to distinguish PCNSL from other central nervous system tumors onlyaccording to their clinical manifestations and radiological findings. Accurate diagnosis is determined bypathological examination. Resection provides no therapeutic benefit but should be reserved for the rarepatients with neurologic deterioration due to herniation. PCNSL suspected in neurologic imaging mustbe confirmed via stereotactic biopsy. Characteristic imaging features should corroborate the diagnosisand surgery should be avoided. The combination of radiotherapy and chemotherapy was feasible and ef-ficient. It improves tumor response rates and survival rates compared with whole brain radiotherapy(WBRT) alone or chemotherapy alone. High-dose MTX-based chemotherapy plus WBRT (30-40Gy)showed significant efficacy for PCNSL.The sequence of radiotherapy and chemotherapy did not signifi-cantly influence the overall survival, but the MST and the 2-year survival rate are significantly differentbetween the two groups.Radiotherapy followed by chemotherapy is superior to chemotherapy followedby radiotherapy.