Given the significant limitations of available literature, central nervous system (CNS) prophylaxis in large B-cell lymphomas remains debatable. Wilson and colleagues provide cautious recommendations, on a case-by-case basis, useful to guide discussion with individual patient. In daily practice, CNS relapse risk, prophylaxis safety and prognosis of CNS recurrence must be considered. Commentary on: Wilson et al. Central nervous system prophylaxis in large B-cell lymphoma: A British Society for Haematology Good Practice Paper. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19686.