Well-established histopathological prognostic factors are lacking in primary central nervous system (CNS) lymphomas (PCNSL). The present study investigated the presence and prognostic role of tumour necrosis (TN) and reactive perivascular T-cell infiltrate (RPVI), defined as a rim of small reactive T-lymphocytes occurring alone or located between the vascular wall and large neoplastic cells, in tumour samples from 100 immunocompetent patients with PCNSL. World Health Organization histotypes of the patients were: 96 diffuse large B-cell lymphomas, two Burkitt-like lymphomas, one anaplastic large T-cell lymphoma and one unclassified B-cell lymphoma. TN was observed in 24 (24%) cases and RPVI in 26 (36%) of 73 assessable cases. Patients with RPVI-positive lesions exhibited a significantly better overall survival (OS) than patients with RPVI-negative lymphoma, particularly among patients treated with high-dose methotrexate-based chemotherapy (3-year OS: 59 +/- 14% vs. 42 +/- 9%, P = 0.02). By contrast, the presence of TN did not demonstrate prognostic significance. Multivariate analysis confirmed an independent association between RPVI and survival. In conclusion, the presence of RPVI is independently associated with survival in PCNSL. This parameter can be easily and routinely assessed at diagnosis on histopathological specimens.