To prospectively investigate the clinical impact of PET/MRI, compared to PET/CT, in a mixed population of cancer patients, and to perform an economic evaluation of PET/MRI. 263 patients (330 same-day PET/CT and PET/MRI examinations) were analyzed. PET/MRI was accurate in 319/330 examinations, and PET/CT in 277/330 examinations; respective accuracies (97.3% vs. 83.9%) differed significantly (P<0.001). Additional findings on PET/MRI had implications for clinical management in 21/263 patients (8.0%). Incremental cost-effectiveness ratios for PET/MRI were 22.47 EUR (~26.28 USD) per percent of diagnostic accuracy, and 37.64 EUR (~44.06 USD) per percent of correctly managed patients.