BACKGROUND: Because standard MRI-based attenuation correction (AC) does not account for the attenuation of photons by cortical bone, PET/MRI may have reduced sensitivity for FDG-avid focal bone lesions (FFBLs). This study evaluates whether MRI-based AC compromises detection of FFBLs, by comparing their conspicuity both quantitatively and qualitatively on PET/MRI versus PET/CT. METHODS: One hundred ninety general oncology patients underwent whole-body PET/CT followed by whole-body PET/MRI, utilizing the same FDG dose. Thirteen patients with a total of 50 FFBLs were identified. Using automated contouring software, a volumetric contour was generated for each FFBL. Adjacent regions of normal background bone (BB) were selected manually. For each contour, SUV-max and SUV-mean were determined. Lesion-to-background SUV ratios served as quantitative metrics of conspicuity. Additionally, two blinded readers evaluated the relative conspicuity of FFBLs on PET images derived from MRI-based AC versus CT-based AC. Visibility of an anatomic correlate for FFBLs on the corresponding CT and MR images was also assessed. RESULTS: SUV-mean was lower on PET/MRI for both FFBLs (-6.5 %, p = 0.009) and BB (-20.5 %, p < 0.001). SUV-max was lower on PET/MRI for BB (-14.2 %, p = 0.002) but not for FFBLs (-6.2 %, p = 0.068). The ratio of FFBL SUV-mean to BB SUV-mean was higher for PET/MRI (+29.5 %, p < 0.001). Forty of 50 lesions (80 %) were visually deemed to be of equal or greater conspicuity on PET images derived from PET/MRI. Thirty-five of 50 FFBLs (70 %) had CT correlates, while 40/50 FFBLs (80 %) had a correlate on at least one MRI sequence. The mean interval from tracer administration to imaging was longer (p < 0.001) for PET/MRI (127 v. 62 min). CONCLUSIONS: Both FFBLs and BB had lower mean SUVs on PET/MRI than PET/CT. This finding was likely in part due to differences in the handling of cortical bone by MRI-based AC versus CT-based AC. Despite this systematic bias, FFBLs had greater conspicuity on PET/MRI, both qualitatively and quantitatively. This difference was likely due to the longer tracer uptake times for PET/MRI, which allowed for more tracer accumulation by FFBLs and more tracer washout from BB. Our results suggest that whole-body PET/MRI and PET/CT provide comparable sensitivity for detection of FDG-avid focal bone lesions.