Abstract: Zhang Qian1, Su Jing, Liu Jianying, Gao Fei, Mei Fang, Zhang Qian 2, Ye Mengmeng, Zhang Wei Department of Pathology, Peking University School of Basic Medical Sciences, Beijing 100191, China （Zhang Q 1, Su J, Liu JY, Gao F, Mei F）; Department of Dermatology, Peking University Third Hospital, Beijing 100191, China （Zhang Q 2）; Department of Pathology, Beijing Changping Hospital, Beijing 102200, China （Ye MM）; Department of Pathology, Beijing Huairou Hospital, Beijing 101400, China （Zhang W） Corresponding author: Liu Jianying, Email: liujianying@bjmu.edu.cn 【Abstract】 Objective To investigate pathological characteristics and differential diagnosis of desmoplastic melanocytic nevus. Methods Four cases of desmoplastic melanocytic nevus were analyzed based on the clinical manifestations and histological, immunohistochemical and fluorescence in situ hybridization （FISH） features. Results Of the 4 cases, 2 were male and 2 were female. Their age ranged from 19 to 30 years with the average age being 26.5 years. The skin lesions were located on the extremities in 3 cases, on the vulva in 1 case. Histologically, the lesions were bilaterally symmetrical intradermal nevus. Nevus cells appeared epithelioid and/or fusiform, some were clustered or scattered in the proliferative fibrous tissue. None of lymphocyte aggregation, necrosis or ulceration was observed. Immunohistochemical examination showed positive staining for S100 and Melan A in 3 cases, positive staining for P16 in 2 cases, Ki?67?labeling index less than 5% in all the 4 cases, and negative staining for factor XIII （FXIII） and CD34 in 2 cases. FISH assay showed no copy?number variations in gene loci 6p25 （RREB1）, 6q23 （MYB）, 6p11.1?q11.1 （Cep6） and 11q13 （CCND1） in desmoplastic melanocytic nevus. Conclusion Desmoplastic melanocytic nevus is a kind of histologically unique, benign melanocytic nevus, and immunohistochemical staining for Ki?67, S?100, Melan A and F??and FISH assay on melanoma can be helpful for the differential diagnosis between cutaneous fibrous histiocytoma and melanoma.