An unmet need remains for a bone graft substitute material that is biocompatible, biodegradable and capable of promoting osteogenesis safely in vivo. The aim of this study was to investigate the use of a novel collagen–hydroxyapatite (CHA) bone graft substitute in the clinical treatment of a mandibular bone cyst in a young horse and to assess its potential to enhance repair of the affected bone. A 2 year-old thoroughbred filly, presenting with a multilobulated aneurysmal bone cyst, was treated using the CHA scaffold. Post-operative clinical follow-up was carried out at 2 weeks and 3, 6 and 14 months. Cortical thickening in the affected area was observed from computed tomography (CT) examination as early as 3 months post-surgery. At 14 months, reduced enlargement of the operated mandible was observed, with no fluid-filled area. The expansile cavity was occupied by moderately dense mineralized tissue and fat and the compact bone was remodelled, with a clearer definition between cortex and medulla observed. This report demonstrates the promotion of enhanced bone repair following application of the CHA scaffold material in this craniomaxillofacial indication, and thus the potential of this material for translation to human applications.