Background: Although potentially curable, primary CNS lymphoma (CNS) is still a therapeutic challenge and only a minority of patients survive longer than 5 years. The factors which define the prognosis of PCNSL patients have only been partially elucidated. A more detailed insight into the parameters which promote long-term survival in PCNSL may allow for more patient-tailored therapies. Methods: We analysed the dataset of patients enrolled into G-PCNSL-SG1, the largest phase 3 study performed in PCNSL evaluating the role of whole-brain radiotherapy after high-dose methotrexate-based chemotherapy. Out of 459 patients with sufficient data quality, we identified 89 patients who had survived for five years or more after surgery and diagnosis of PCNSL. This long-term survival (LTS) cohort was compared with two different reference groups: first, patients who had died within one year of diagnosis for any reason (control 1 = C1 patients) and second, all patients who had survived for more than 1 year, but who did not reach a survival of 5 years from diagnosis (control 2 = C2 patients). Patients censored (i.e. alive but without further follow-up) before 5 years of follow-up were excluded. Within the LTS group, survival after 5 years was analysed using the Kaplan Meier method. Results: We compared baseline characteristics and treatment of the 89 patients surviving for 5 years or more with the C1 and C2 control populations. Patients within the LTS cohort were younger and had a higher performance score at diagnosis. Furthermore, they had less frequently multiple tumor manifestations, a better renal function and were less often affected by cardiovascular disease. High-dose methotrexate-based treatment resulted in a higher complete response rate and was associated with less toxicity, particularly a reduced frequency of myelosuppression. Within the group of LTS patients, age at diagnosis was the only prognostic factor for conditional survival from 5 years on. Conclusions: Within this large patient population, survival of 5 years or more was reached by approximately a fifth of the patients. Young and fit patients with single lesions are most likely to survive for 5 years or more following diagnosis of PCNSL.