Background Bone marrow assessment is an important part in the Ann Arbor staging system in lymphoma. It is done routinely through posterior iliac crest bone marrow biopsy (BMB) which is an invasive technique with limited examination of one site. 18F-FDG PET/CT is now used for staging of lymphoma. The purpose of this study was to compare the sensitivity of PET/CT and BMB in detecting bone marrow infiltration (BMI) in lymphoma and determine agreement between both in assessing bone marrow and whether we can evaluate the bone marrow by PET/CT without the need of the routine BMB. Results PET/CT detected 24 (16.5%) cases with positive BMI that were missed by BMB. BMB detected only 2 (1.4%) cases that were missed by PET/CT. The PET/CT showed a higher sensitivity of 95.6% than BMB 46.7% in detecting BMI in lymphoma. We found a moderate agreement between PET/CT and BMB results in the whole cohort using Cohen’s k computation. It was found that 0.47 with p value less than 0.0001. Conclusions PET/CT can detect more bone marrow involvement in lymphoma compared with BMB. It can replace the routine invasive BMB in many cases, especially those showing multifocal uptake in both Hodgkin and non-Hodgkin lymphoma. PET/CT can also help to guide the site of the biopsy in some cases. Iliac crest BMB is still needed in cases showing diffuse FDG uptake to differentiate malignant uptake from reactive hyperplasia, and in those with limited FDG avidity and in some cases with negative uptake to exclude early infiltration if management will differ.