The aims in treating patients diagnosed with critical-sized bone defects resulting from bone cysts are to replace the lost bone mass after its removal and to restore function. The standard treatment is autologous or allogeneic bone transplantation, notwithstanding the known consequences and risks due to possible bone infection, donor site morbidity, bleeding and nerve injury and possible undesirable immune reactions. Additionally, allogeneic grafts are inhomogeneous, with a mosaic of components with difficult-to-predict regenerative potential, because they consist of cancellous bone obtained from different bones from various cadavers. In the present study, a 22-year-old patient with a history of right humerus fracture due to bone cysts was diagnosed with recurrent cystic lesions based on X-ray results. The patient qualified for an experimental program, in which he was treated with the application of a bioresorbable polylactide hybrid sponge filled with autologous platelet-rich plasma. Computed tomography and magnetic resonance imaging performed 3, 6, and 36 months after surgery showed progressive ossification and bone formation inside the defect cavity in the humerus. Three years after treatment with the bone substitute, the patient is pain free, and the cystic lesions have not reoccurred.