To determine whether the current 18 F-FDG PET response criterion for skeletal involvement in Hodgkin lymphoma (HL) is suitable, we performed a systematic evaluation of the different types of skeletal involvement and their response on PET after 2 cycles of chemotherapy (PET-2). A secondary objective was to observe the influence of the initial uptake intensity (measured as qPET) and initial metabolic tumor volume (MTV) of skeletal lesions on the PET-2 response. Methods: The initial PET scans of 1,068 pediatric HL patients from the EuroNet-PHL-C1 trial were evaluated for skeletal involvement by central review. Three types of skeletal lesions were distinguished: PET-only lesions (those detected on PET only), bone marrow (BM) lesions (as confirmed by MRI or BM biopsy), and bone lesions. qPET and MTV were calculated for each skeletal lesion. All PET-2 scans were assessed for residual tumor activity. The rates of complete metabolic response for skeletal and nodal involvement on PET-2 were compared. Results: Of the 1,068 patients, 139 (13%) showed skeletal involvement (44 PET-only, 32 BM, and 63 bone). Of the 139 patients with skeletal involvement, 101 (73%) became PET-2–negative in the skeleton and 94 (68%) became PET-2–negative in the lymph nodes. The highest number of PET-2–negative scans in the skeleton was 42 (95%) in the 44 PET-only patients, followed by 22 skeletal lesions (69%) in the 32 BM patients and 37 (59%) in the 63 bone patients. Lesions that became PET-2–negative showed a lower initial median qPET (2.74) and MTV (2 cm 3 ) than lesions that remained PET-2–positive (3.84 and 7 cm 3 , respectively). Conclusion: In this study with pediatric HL patients, the complete response rate for skeletal involvement on PET-2 was similar to that for nodal involvement. Bone flare seemed to be irrelevant. Overall, the current skeletal PET response criterion—comparison with the local skeletal background—is well suited. The initial qPET and MTV of skeletal lesions were predictive of the PET-2 result. Higher values for both parameters were associated with a worse PET-2 response.