Purpose <p>Systemic histiocytoses, including Erdheim-Chester disease, Langerhans cell histiocytosis, and Rosai-Dorfman disease, are rare multisystem disorders requiring accurate whole-body assessment for staging, treatment planning, and follow-up. While 18F-FDG PET/CT is the current reference imaging modality, PET/MRI may improve lesion detection and characterization owing to its superior soft-tissue contrast and lower radiation burden.</p> Methods <p>In this prospective single-centre study, 15 patients with systemic histiocytosis underwent sequential whole-body 18F-FDG PET/CT and PET/MRI after a single radiotracer injection. Images were independently assessed by two nuclear medicine physicians and one radiologist, with consensus evaluation of lesion detection, anatomical delineation, metabolic uptake, and disease extent.</p> Results <p>PET/CT and PET/MRI were concordant in 14/15 patients (93%). PET/MRI detected additional lesions or provided improved characterisation of known involved sites in 5/15 patients (33%), particularly in the central nervous system, lymph nodes, and bone marrow. Overall, 37 histiocytosis-attributed lesion sites were identified; PET/MRI detected all 37, whereas PET/CT detected 34. PET/MRI provided higher lesion delineation scores in 60% of cases and improved lesion characterisation in 33%. A brainstem lesion detected only by PET/MRI, in a patient with progressive cognitive deterioration, prompted re-evaluation of the therapeutic plan. PET/CT showed better performance for pulmonary lesion assessment.</p> Conclusion <p>18F-FDG PET/MRI provided incremental diagnostic value over PET/CT in systemic histiocytoses, particularly for lesion detection and characterization in anatomically complex regions. PET/MRI may be especially useful in patients requiring repeated imaging follow-up, although PET/CT remains advantageous for lung evaluation.</p>