A 43-year-old female patient was diagnosed with myxoid liposarcoma G2 at the left distal femur. After wide resection with periosteal stripping and prophylactic plating, the patient underwent radiotherapy. Follow-up was uneventful until 83 months after definite surgery, a novel intramedullary lesion with extraosseous component at the irradiated distal left femur was found. Initial computed tomography (CT)-guided biopsy (carried out through extensor mechanism) remained inconclusive. Open re-biopsy revealed a secondary, radiation-induced osteosarcoma G3. After careful patient counselling, she underwent limb-salvage surgery with wide resection of the distal femur and tumour-endoprosthetic reconstruction. Three months after primary diagnosis, and 3 months after last surgery, the patient is receiving her eighth chemotherapeutic cycle (EURO BOSS protocol). Her limb function is limited with active flexion up to 60°, but no active extension.