Our purpose was to investigate differences between PET/MRI and PET/CT in lesion detection and classification in oncologic whole-body examinations and to investigate radiation exposure differences between the 2 modalities. Methods: In this observational single-center study, 1,003 oncologic examinations (918 patients; mean age, 57.8 ± 14.4 y) were included. Patients underwent PET/CT and subsequent PET/MRI (149.8 ± 49.7 min after tracer administration). Examinations were reviewed by radiologists and nuclear medicine physicians in consensus. Additional findings, characterization of indeterminate findings on PET/CT, and missed findings on PET/MRI, including their clinical relevance and effective dose of both modalities, were investigated. The McNemar test was used to compare lesion detection between the 2 hybrid imaging modalities (P , 0.001, indicating statistical significance). Results: Additional information on PET/ MRI was reported for 26.3% (264/1,003) of examinations, compared with PET/CT (P , 0.001). Of these, additional malignant findings were detected in 5.3% (53/1,003), leading to a change in TNM staging in 2.9% (29/1,003) due to PET/MRI. Definite lesion classification of indeterminate PET/CT findings was possible in 11.1% (111/1,003) with PET/MRI. In 2.9% (29/1,003), lesions detected on PET/CT were not visible on PET/MRI. Malignant lesions were missed in 1.2% (12/1,003) on PET/MRI, leading to a change in TNM staging in 0.5% (5/1,003). The estimated mean effective dose for whole-body PET/CT amounted to 17.6 ± 8.7 mSv, in comparison to 3.6 ± 1.4 mSv for PET/MRI, resulting in a potential dose reduction of 79.6% (P , 0.001). Conclusion: PET/MRI facilitates staging comparable to that of PET/CT and improves lesion detectability in selected cancers, potentially helping to promote fast, efficient local and whole-body staging in 1 step, when additional MRI is recommended. Furthermore, younger patients may benefit from the reduced radiation exposure of PET/MRI.