The aim of this preliminary study was to evaluate the clinical effectiveness of the association of amelogenins and autologous bone graft in the management of mandibular class II furcation defects. This randomized case-controlled study was conducted on 2 patients who presented 2 contralateral mandibular buccal class II furcation lesions. One defect was treated by amelogenins and autologous bone graft (test site) and the other one by open flap debridement (control site). At baseline and at 12 months postoperatively, the full-mouth plaque score (FMPS) and the full-mouth bleeding score (FMBS), the probing depth (PD), the clinical attachment level (CAL) and the recession (REC) were recorded and a periapical radiograph of the selected area was taken. In addition, at 12 months a surgical re-entry was performed. Test sites had a greater horizontal PD reduction and radiographic bone filling compared to control sites. None of the treated sites achieved complete furcation closure. At the time of re-entry, furcations treated by amelogenins were partially filled by newly formed not soundable hard tissue, while furcations treated by conventional flap surgery were filled by epithelial and connective tissue. These findings suggest that the treatment of mandibular class II furcations by amelogenins and autologous bone graft may result in a significant clinical improvement. Further long-term studies conducted on a larger sample size are therefore needed to confirm our results.