To investigate the clinicopathological features, and mutations of NRAS, KRAS, BRAF and MAP2K1 genes in extranodal Rosai-Dorfman disease (RDD).The clinic opathological features of 27 patients with extranodal RDD were retrospectively analyzed, and the NRAS, KRAS, BRAF and MAP2K1 genes mutation were detected by Sanger sequencing.The male to female ratio was 1.7:1. The average age was 46.9 years. There were skin lesions in 12 cases (44.4%) and head and neck lesions in 8 cases (29.6%). Microscopically, those patients with skin RDD had lesions characterized by clear and dark intervals and obvious emperipolesis, while in other parts, the background was more complex. About 21.1% (4/19) had mutations, including 3 mutations in NRAS 2 exon and 1 mutation in KRAS 2 exon. Two of the three NRAS mutations were located in the skin, accounting for 20% (2/10) of skin RDD.Extranodal RDD was more common in males than in females, and might occur in all ages, with a greater incidence in skin, head, and neck. Besides the obvious microscopic characteristics in those with skin RDD, the background of other parts was complex and easily missed or misdiagnosed. Some RDD with gene mutations, mainly in NRAS 2 exon, especially in skin RDD, support partial RDD is a clonal disease.© 2022 Tang et al.