BACKGROUND: To analyze the regional composition of bone marrow (BM) in correlation with metabolic activity and diffusivity using simultaneous positron emission tomography (PET)/MRI. METHODS: Retrospective analysis of 18F-FDG-PET/MR scans of 110 patients was performed. A three-dimensional gradient-echo sequence with Dixon-based fat-water separation was used for fat quantification. Dixon images, diffusion-weighted images (DWI) and 18F-FDG-PET were co-registered. Mean values of fat fraction (FF), standardized uptake value (SUV), and apparent diffusion coefficient (ADC) of BM were measured in different anatomical regions. Correlation of FF, SUV, and ADC and association of BM fat content and metabolic activity with anthropometric data was analyzed (Pearson). BM fat content and metabolic activity was compared in patients with and without chemotherapy (t-test). RESULTS: Regional differences in BM were found with highest fat content (93 ± 8%) and lowest ADC (0.22 ± 0.18 × 10(-3) mm(2) /s) in the peripheral skeleton and highest SUV in the spine (1.77 ± 0.6). There was a significant inverse correlation between FF and SUV (r = -0.73; P < 0.0001) and a significant inverse correlation between FF and ADC (r = -0.62; P < 0.0001). In patients with chemotherapy, a tendency to higher fat content and lower metabolic activity was observed in the proximal skeleton, although no statistical significance was reached. CONCLUSION: BM shows distinct regional variations in FF, SUV, and ADC. The inverse correlation of FF and SUV in BM suggests that BM adipose tissue does not have a comparable high metabolic activity as brown adipose tissue.