BACKGROUND: The optimal timing of corticosteroid (CS) treatment in patients with primary central nervous system (CNS) lymphoma (PCNSL) remains controversial. While poor clinical presentation may justify early treatment with CS, this may ultimately result in reduced concentrations of chemotherapeutic agents via perturbations in the permeability of the blood-brain barrier. OBJECTIVE: To investigate whether early CS exposure is associated with beneficial outcomes and/or reduced occurrence of adverse events as opposed to delayed/concomitant administration. METHODS: Herein we performed a retrospective observational analysis using patients that were prospectively entered into a database. All patients whom were admitted to the University Hospital between 2009 and 2015 with newly diagnosed PCNSL were included within our study. RESULTS: Our cohort included 50 consecutive patients diagnosed with PCNSL; of these, in 30 patients CS administration was initiated prior to chemotherapy (early), whilst in the remaining 20 patients CS administration was initiated concomitantly with their chemotherapeutic regimen (concomitant). Within the early vs concomitant CS administration groups, no significant differences were observed with regard to progression-free survival (PFS) (P =. 81), overall survival (OS) (P =. 75), or remission (P =. 68; odds ratio 0.76 and confidence interval [95%] 0.22-2.71). Critically, the timing of CS initiation was not associated with either PFS (P =. 81) or PFS (P =. 75). CONCLUSION: Early CS administration was not associated with a deterioration in response to chemotherapy, PFS, or OS. As such, administration of CS prior to initiation of chemotherapy is both reasonable and safe for patients with newly diagnosed PCNSL.