Heterologous differentiation in adipocytic tumors is a rare phenomenon. Only 4 cases of myxoid liposarcoma (MLS) with cartilaginous differentiation were thus far reported without confirmatory molecular assays. We describe a primary MLS with chondroid differentiation that affected the left thigh of a 47-year-old man. Histologically, multiple sharply demarcated chondroid nodules were embedded among the classic MLS area. By reverse transcription-polymerase chain reaction, the identical type II TLS-CHOP fusion gene transcripts were detected in both the liposarcomatous and microdissected chondroid tumor cells. Our case confirms the actual existence of MLS with cartilaginous differentiation and the neoplastic nature of chondroid component.