Background and Aims: 40-50% of patients with primary central nervous system lymphoma (PCNSL) suffer treatment failure after methotrexate (MTX)-based chemotherapy. While whole brain radiation therapy (WBRT) has been reported as an effective salvage modality in this context, the combination of MTX and WBRT causes synergistic neurotoxic effects. Here we investigated the use of radiosurgery as an alternate salvage modality. Methods: We reviewed the records of immunocompetent adults with pathology-confirmed PCNSL who underwent radiosurgery as salvage therapy at the Massachusetts General Hospital between 1993 and 2007. Thirteen salvage radiosurgeries were performed in 7 PCNSL patients. Results: Lesion size ranged from 0.2 to 3.1 (median 0.31) cm 3. Doses were prescribed to the periphery of the lesion and normalized to the 90% isodose line (12-16, median 15 Gy). Follow-up ranged from 18 to 103 (median 29) months. According to the Macdonald criteria, complete radiographic response was observed in 11/13 lesions, stable disease in 1 lesion and disease progression in another lesion. 3/7 patients required multiple radiosurgeries for relapse outside the initial radiosurgery volume. Focal FLAIR signal abnormalities outside the irradiated volume were seen in all cases, though only 2/7 patients developed the type of diffuse leukoencephalopathy that is associated with MTX + WBRT therapy. Conclusion: This series suggests that radiosurgery is an effective and well-tolerated salvage therapy for patients with small recurrent PCNSL lesions.