Patients diagnosed with diffuse large-cell lymphoma, peripheral T-cell non-Hodgkin's lymphoma or mantle cell lymphoma (either with a high serum lactate dehydrogenase level), more than one extranodal site, or who are a high risk according to the international Prognostic Index, should receive central nervous system prophylaxis either with intrathecal or high-dose systemic chemotherapy. The appropriateness of the same prophylaxis at relapse needs to be addressed in further studies.