Currently, bone marrow (BM) biopsy (BMB) is recommended in the initial staging of patients with the presumed primary central nervous system (CNS) lymphoma (PCNSL). However, the added value of BMB in the era of positron emission tomography(PET-CT) has been challenged in other lymphoma subtypes. We analyzed BM findings in patients with biopsy-proven CNS lymphoma and a negative PET-CT scan for disease outside CNS. A comprehensive Danish population-based registry search was performed to identify all patients with CNS lymphoma of diffuse large B cell lymphoma (DLBCL) histology with available BMB results and staging PET-CT without systemic lymphoma. A total of 300 patients fulfilled the inclusion criteria. Of them, 16% had a previous history of lymphoma, while 84% were diagnosed with PCNSL. None of the patients had DLBCL in the BM. A minority (8.3%) had discordant BMB findings, mainly low-grade histologies that did not influence treatment choice in any case. In conclusion, the risk of overlooking concordant BM infiltration in patients with CNS lymphoma of DLBCL histology and negative PET-CT scan is negligible. As we did not find any patient with DLBCL in the BMB, our results suggest that BMB can be safely omitted in the diagnostic workup in patients with CNS lymphoma and a negative PET-CT.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00277-023-05282-7.