PURPOSE: (18)F-FDG PET has been successfully evaluated in the management of Hodgkin's lymphoma (HL) and the most recent international guidelines recommended (18)F-FDG PET for initial staging and final therapeutic assessment. However, (18)F-FDG PET diffuse bone marrow uptake (BMU) and splenic uptake (SU) are frequently observed at the initial imaging and remain difficult to analyse. The aim of this retrospective study was to evaluate the significance of (18)F-FDG diffuse BMU and SU in initial staging of HL. METHODS: A total of 106 patients (median age: 31 years, range: 9-81, 51 female, 55 male) underwent (18)F-FDG PET/CT for initial staging of HL. BMU level was assessed visually according to liver uptake (1 = below liver uptake, 2 = corresponding to liver uptake, 3 = above liver uptake) and semi-quantitatively using the maximum standardized uptake value (SUV(max)) measured in the sacral area. SU was assessed visually according to liver uptake (1 = below liver uptake, 2 = corresponding to liver uptake, 3 = above liver uptake). These data were compared with the patient's characteristics including sex, age, Ann Arbor staging, bulky disease (tumour burden > 10 cm), presence of B symptoms, bone foci on PET (n = 106), bone marrow involvement (BMI) on biopsy (n = 75), leukocyte count (n = 74), lactic dehydrogenase (LDH) (n = 87), C-reactive protein (CRP) (n = 83) and fibrinogen (n = 60). Univariate and multivariate analyses were performed. RESULTS: Multivariate analysis found an independent correlation between BMU visual grading and CRP level (p = 0.007). For semi-quantitative BMU evaluation, multivariate analysis found an independent correlation between sacral SUVs and CRP level (p = 0.032) and Ann Arbor stage (p = 0.005). No BMI was found in patients who presented with SUV(max) below 3.4. For splenic evaluation, multivariate analysis found an independent correlation between SU and splenic foci (p = 0.034). No statistical link was found between SU and inflammatory markers. CONCLUSION: Our study demonstrates that diffuse BMU at initial staging of HL could be due to bone marrow involvement but more likely to bone marrow inflammatory change and that diffuse SU in contrast is probably more associated with disease involvement than with inflammatory change.