The aim of this study was to prospectively compare whole-body PET/MR imaging and PET/CT, qualitatively and quantitatively, in oncologic patients and assess the confidence and degree of inter-and intraobserver agreement in anatomic lesion localization. Methods: Fifty patients referred for staging with known cancers underwent PET/CT with low-dose CT for attenuation correction immediately followed by PET/MR imaging with 2-point Dixon attenuation correction. PET/CT scans were obtained according to standard protocols (56 6 20 min after injection of an average 367 MBq of 18 F-FDG, 150 MBq of 68 Ga-DOTATATE, or 333.8 MBq of 18 F-fluoro-ethyl-choline; 2.5 min/bed position). PET/MR was performed with 5 min/bed position. Three dual-accredited nuclear medicine physicians/radiologists identified the lesions and assigned each to an exact anatomic location. The image quality, alignment, and confidence in anatomic localization of lesions were scored on a scale of 1-3 for PET/CT and PET/MR imaging. Quantitative analysis was performed by comparing the standardized uptake values. Intraclass correlation coefficients and the Wilcoxon signed-rank test were used to assess intra-and interobserver agreement in image quality, alignment, and confidence in lesion localization for the 2 modalities. Results: Two hundred twenty-seven tracer-avid lesions were identified in 50 patients. Of these, 225 were correctly identified on PET/CT and 227 on PET/MR imaging by all 3 observers. The confidence in anatomic localization improved by 5.1% when using PET/MR imaging, compared with PET/CT. The mean percentage interobserver agreement was 96% for PET/CT and 99% for PET/MR imaging, and intraobserver agreement in lesion localization across the 2 modalities was 93%. There was 10% (5/50 patients) improvement in local staging with PET/MR imaging, compared with PET/CT. Conclusion: In this first study, we show the effectiveness of whole-body PET/MR imaging in oncology. There is no statistically significant difference between PET/MR imaging and PET/CT in respect of confidence and degree of inter-and intraobserver agreement in anatomic lesion localization. The PET data on both modalities were similar; however, the observed superior soft-tissue resolution of MR imaging in head and neck, pelvis, and colorectal cancers and of CT in lung and mediastinal nodal disease points to future tailored use in these locations.