The diagnosis of Rosai-Dorfman disease (RDD) was first described in 1969 and classified as a non-Langerhans cell histiocytosis. RDD is a rare benign lymphoproliferative disease of an unknown cause [1,2,3,4]. The disease is characterized by painless massive cervical lymphadenopathy associated with fever, weight loss, and night sweats in most patients3. Lymph nodes of the mediastinum, abdominal cavity, and pelvic cavity may also be involved4. Studies have shown that over 40% of cases involve extranodal sites, including the nasal cavity (11%), orbital tissue (11%), skin (10%), bone (5–10%), central nervous system (5%), lung, and salivary glands [5,6,7]. However, it is very rare to involve only an extranodal site, especially isolated thymic RDD [8,9,10]. Therefore, a thymic mass is initially diagnosed as thymic malignancy or lymphoma according to the local infiltration in clinical practice. Immunohistochemistry (IHC) remains the primary approach for the diagnosis of RDD, especially when the characteristic histiocytes show positive staining of S-100 protein, weak positive staining of CD68 protein, and negative staining of CD1a. However, 18F-FDG PET/CT, which sensitively detects metabolically active lesions, may not specifically distinguish benign and malignant thymic lymphoproliferative disorders. Ruth Lim et al. have found that RDD lesions exhibit higher 18F-FDG uptake due to increased glucose metabolism of the proliferating histiocytes and greater infiltration of inflammatory cells than tumor cells [4,10]. In the present work, we reported a rare case of thymic RDD that was difficult to distinguish from malignant lesions.