Objective To investigate the clinicopathologic features and differential diagnosis of atypical fibroxanthoma (AFX). Methods A total of 5 AFX cases were collected from Jan. 2016 to Dec. 2021 in The Second Affiliated Hospital of Nanchang University. The epidemiological characteristics, pathological morphology and immunohistochemical characteristics were analyzed retrospectively. Results Among the 5 AFX patients, there were 3 males and 2 females, with an average age of 58.6 years. AFX showed superficial skin nodules with a maximum diameter of 0.9-2.5 cm. Microscopically, the morphology of the tumor cells varied largely, mainly characterized by spindle cells and epithelioid cells, mixed with mononuclear and multinucleated tumor giant cells, and mitotic images were easy to see. Among them, 1 case contained pigment, 1 case combined with basal cell carcinoma, and 1 case had many inflammatory cells. Immunohistochemical markers showed that AFX mainly expressed vimentin and CD10; cytokeratin, epithelial membrane antigen and CD68 were expressed in some cases; and Ki-67 proliferation index was high in all patients. Local resection of skin mass was performed in all the 5 cases, and postoperative radiotherapy was performed in only 1 case. There were no local recurrence or metastasis during follow-up until May 2022. Conclusion AFX is rare in clinic and can easily be confused with malignant tumors under microscope. Immunohistochemistry indexes including CD10 are helpful for its diagnosis and differential diagnosis.