Background <p>Non-small cell lung cancer (NSCLC) is a common neoplasm with poor prognosis in advanced stages. The clinical work-up in patients with locally advanced NSCLC mostly includes ¹⁸F-fluorodeoxyglucose positron emission tomography computed tomography (¹⁸F-FDG PET/CT) because of its high sensitivity for malignant lesion detection; however, specificity is lower. Diverging results exist whether whole-body MRI (WB-MRI) improves the staging accuracy in advanced lung cancer. Considering WB-MRI being a more time-consuming examination compared to brain MRI, it is important to establish whether or not additional value is found in detecting and characterizing malignant lesions. The purpose of this study is to investigate the value of additional whole-body magnetic resonance imaging, instead of only brain MRI, together with ¹⁸F-FDG PET/CT in staging patients with advanced NSCLC planned for curative treatment.</p> Material and methods <p>In a prospective single center study, 28 patients with NSCLC stage 3 or oligometastatic disease were enrolled. In addition to ¹⁸F-FDG PET/CT, they underwent WB-MRI including the thorax, abdomen, spine, pelvis, and contrast-enhanced examination of the brain and liver. ¹⁸F-FDG PET/CT and WB-MRI were separately evaluated by two blinded readers, followed by consensus reading in which the likelihood of malignancy was assessed in detected lesions. Imaging and clinical follow-up for at least 12 months was used as reference standard. Statistical analyses included Fischer’s exact test and Clopped-Pearson.</p> Results <p>28 patients (mean age ± SD 70.5 ± 8.4 years, 19 women) were enrolled. WB-MRI and FDG-PET/CT both showed maximum sensitivity and specificity for primary tumor diagnosis and similar sensitivity (<i>p</i> = 1.00) and specificity (<i>p</i> = 0.70) for detection of distant metastases. For diagnosis of lymph node metastases, WB-MRI showed lower sensitivity, 0.65 (95% CI: 0.38–0.86) than FDG-PET/CT, 1.00 (95% CI: 0.80-1.00) (<i>p</i> &lt; 0.05), but similar specificity (<i>p</i> = 0.59).</p> Conclusions <p>WB-MRI in conjunction with ¹⁸F-FDG PET/CT provides no additional value over MRI of the brain only, in staging patients with advanced NSCLC.</p> Trial registration <p>Registered locally and approved by the Uppsala University Hospital committee, registration number ASMR020.</p>