ABM/P-15 is a combination of a natural anorganic bovine-derived hydroxyapatite matrix (ABM) and a synthetic cell-binding peptide (P-15; PepGen P-15) that has shown the capacity to encourage substantial clinical fill of periodontal infrabony defects. Human histology following its use has not been evaluated on pathologic root surfaces. A maxillary lateral incisor with advanced adult periodontitis that was treatment planned for extraction was treated with sulcular incisions, full-thickness flap reflection, debridement of granulomatous tissue from the defect, placement of a notch in the root at the apical extent of calculus, mechanical root planing, brief cleansing with citric acid, grafting with ABM/P-15, wound closure with sutures, and placement of a periodontal dressing. Biweekly to monthly recalls were made until removal of a small block section biopsy at about 6 months. Histologic evaluation of the region coronal to the apical edge of the calculus notch showed evidence of regeneration (new cementum, bone, and periodontal ligament). Graft particles were still present at 6 months, but no evidence of root resorption, ankylosis, or untoward inflammation was seen. This case report fulfills the proof of principle that use of ABM/P-15 can result in periodontal regeneration on previously diseased root surfaces in humans.