This retrospective case series describes a layered regenerative approach for five Class III and one borderline Class IV furcation, involving treatment consisting of root management that included conditioning with tetracycline solution followed by the topical application of recombinant platelet-derived growth factor BB. A composite allograft with mesenchymal stem cells was subsequently placed into the furcation and covered by a barrier derived from human amnion-chorion with flaps advanced to completely cover the site. Three furcations, including the one diagnosed as Class IV, had complete closure, two were converted to Class I, and in one instance, there was no improvement. This regenerative algorithm for mandibular Class III furcations may present the potential to save these teeth by altering the prognosis, which has traditionally been poor to hopeless, resulting in many of these teeth routinely being extracted.