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To date, there is no relevant data supporting the role of salvage radiotherapy (sRT) in patients with refractory or relapsed primary central nervous system lymphoma (PCNSL). Herein, we aimed to investigate the impact of sRT in patients with refractory or relapsed PCNSL following upfront HD-MTX. We retrospectively reviewed 89 patients who had refractory (n = 16) or recurrent disease after an initial favorable response (n = 73); among them, 41 were treated with sRT and 48 were treated without sRT (nRT). Event-free survival (rEFS) and overa