Modern chemotherapy protocols have improved the prognosis for acute lymphoblastic leukaemia (ALL), one of the most common paediatric malignancies, but their high-dose corticosteroids lead to osteonecrosis in up to 9% of ALL patients. A 13.5-year-old female patient developed massive osteonecrosis of the right knee after successful ALL treatment. She presented at the age of 17.5 years as a candidate for knee arthroplasty after conservative treatment had failed. Magnetic Resonance Imaging (MRI) revealed severe osteonecrosis, with the cartilage layer of the medial femoral condyle completely detached from the bone. We preferred to attempt a two-step biological reconstruction in this young patient, with arthroscopy of the right knee joint and removal of the dissected cartilage layer of the medial condyle. Matrix-assisted autologous chondrocyte implantation (MACI) was performed with harvested chondrocytes after imaging had indicated vital bone remodelling. Rehabilitation was according to MACI guidelines and after 5.5 years, the patient shows continuous clinical improvement and is satisfied with the result. The Lysholm score improved from 45 to 99 and Tegner's activity score from 1 to 4. MRI follow-up showed a solid cartilage layer covering the medial condyle as a result of bone and chondral regeneration. Even if this approach had failed, bone remodelling would have still provided better conditions for knee arthroplasty.