Objective: To investigate the histopathology and characteristics of recurrent cases of liposarcoma. Methods: The clinical data of 102 patients diagnosed with liposarcoma were collected. The relevant cases were analyzed by routine histological observation and immunohistochemical expression, and the prognosis was followed up. FISH molecular detection was for difficult cases and final diagnosis. Results: CDK4 and MDM2 were mainly expressed in highly differentiated, dedifferentiated and not otherwise specified subtypes of liposarcoma (positive rates were 91.1% and 85.7%, respectively), but were rarely expressed in myxoid and pleomorphic subtypes. The overall positive rate of S-100 in liposarcoma was 52%, while the positive rates in myxoid and pleomorphic subtypes were 32.4% and 44.4%, respectively. MDM2 gene amplification was detected in 10 highly differentiated liposarcomas and 2 dedifferentiated liposarcomas by FISH. DDIT3 gene rearrangement was detected in 8 cases of myxoid liposarcoma by FISH. The tumors were prone to recurrence, with recurrence intervals ranging from 5 to 30 months, but fewer metastases, with 4 patients dying. Approximately 32% (8 cases) of recurrent cases showed histological transformation, and 5 cases of histopathological malignancy were higher than the primary tumors. Conclusion: The combination of CDK4 and MDM2 can help to diagnose, and the S-100 can be used as a supplementary reference. For difficult cases, FISH molecular detection can make a definite diagnosis. The malignant degree of recurrent tumors is not all improved compared with the primary tumors. Some highly differentiated tumors proliferate slowly.