To investigate the clinicopathological characteristics and diagnosis of atypical fibroxanthoma (AFX) and undifferentiated pleomorphic sarcoma (UPS), in order to raise awareness and differential diagnosis of them. Methods Excised dermatological specimens diagnosed as AFX, superficial malignant fibrous histiocytoma (superficial MFH), MFH and UPS from 2015 to 2020 were retrospectively reviewed on the clinical data, histological and immunohistochemical features. They were classified and further analyzed for recurrence risk. Results Four cases of AFX were aged from 73 to 89 years old. They were 2 males and 2 females. The lesions were located on the head and face. Microscopically, the tumor cells showed obvious pleomorphism, with spindle cells, epithelioid cells and multinucleated giant cells disordered. The 22 cases of UPS were aged from 21 to 82 years old, including 20 males and 2 females. The lesions were mainly located in the extremities, chest and abdomen, and the microscopic morphology was similar to AFX. Immunohistochemical results of AFX and UPS were similar, and there was no significant difference in the expression of different cell types and infiltration levels. Among recurrent cases, those with spindle cell predominance had more frequent local recurrence than pleomorphic/mixed cell predominance (P＜0.05). Conclusion The microscopic morphology and immunolabeling results of AFX and PDS/UPS are similar, but the clinical onset age and site are different, the latter showed obvious malignant indications such as infiltration, necrosis and vascular invasion in pathology. Differentiation from other similar skin spindle cell tumors depends on histopathology and adequate immunomarker tests. Tumor size and margin are useful prognostic indicators. In addition, the spindle cell pattern of AFX and UPS appears to be more aggressive and prone to relapse. Grouping tumors according to microscopic basis may be helpful for prognostic judgment.