RATIONALE: Positron Emission Tomography/Computed Tomography (PET/CT)-ascertained bone marrow involvement (BMI) constitutes the single most important reason for upstaging by PET/CT in Hodgkin lymphoma (HL). However, BMI assessment in PET/CT can be challenging. This study analysed the clinico-pathological correlations and prognostic meaning of different patterns of bone marrow (BM)-Fluorodeoxyglucose (FDG)-uptake in HL. PATIENTS AND METHODS: 180 newly diagnosed early unfavourable and advanced stage HL patients, all scanned at baseline and after 2 Adriamycin-Bleomycin-Vinblastine-Dacarbazine (ABVD) courses with FDG-PET, enrolled in two International studies aimed at assessing the role of interim PET scan in HL, were retrospectively included. Patients were treated with ABVD x 4-6 cycles and involved-field radiation when needed, and no treatment adaptation on interim PET scan was allowed. Two blinded reviewers independently reported the scans. RESULTS: Thirty-eight patients (21.1%) had focal lesions (fPET+), 10 of them with a single (unifocal) and 28 with multiple (multifocal) BM lesions. Fifty-three (29.4%) had pure strong (> liver) diffuse uptake (dPET+) and 89 (48.4%) showed no or faint (≤ liver) BM uptake (nPET+). BM biopsy (BMB) was positive in 6/38 (15.7%) of fPET+, in 1/53 (1.9%) of dPET+ and in 5/89 (5.6%) of nPET+. dPET+ was correlated with younger age, higher frequency of bulky disease, lower hemoglobin levels, higher leucocyte counts and similar diffuse uptake in the spleen. Patients with pure dPET+ had an identical 3-year Progression Free Survival (3Y-PFS) to patients without any FDG uptake (82.9% and 82.2%, respectively P = 0.918). However patients with fPET+ (either unifocal or multifocal) had a 3-Y-PFS significantly inferior to patients with dPET+ and nPET+ (66.7% and 82.5%, respectively, P = 0.03). The kappa-values for inter-observer agreement were 0.84 for focal uptake and 0.78 for diffuse uptake. CONCLUSION: We confirmed that FDG-PET scan is a reliable tool for BMI assessment in HL and BMB is no longer needed for routine staging. Moreover, the inter-observer agreement for BMI in this study proved excellent and only focal FDG BM uptake should be considered as a harbinger of HL.