Primary central nervous system lymphoma (PCNSL) is a rare form of extra-nodal non-Hodgkin lymphoma. Although recommendations for first-line treatment usually incorporate high-dose methotrexate, there is substantial heterogeneity in the types of salvage therapies used at relapse. Phase II data supported the use of temozolomide as a well-tolerated treatment modality in this setting. Therefore, we reviewed the treatment and outcomes of patients with relapsed PCNSL who were treated with salvage temozolomide at our institution. Seven patients were treated with salvage temozolomide between January 2000 and May 2011. The objective response rate was 14%. Progression-free survival was 2 months (95% confidence interval [CI]: 0-5.9) and median overall survival was 4 months (95% CI: 0-13). Toxicity was mild, with one episode of grade 3 neutropenia during 25 cycles of chemotherapy. Although these results are consistent with previous phase II results, the outcomes for these patients remain extremely poor. The low toxicity of temozolomide raises the possibility of combining temozolomide with other chemotherapeutic agents or targeted agents in future clinical trials.