We report the case of a 74-year-old white male patient who had worn an overdenture for the previous 6 years, retained by 4 screwed implants and a bar, who presented with an exophytic multilobed lesion of 2.5×2.0 cm on the anterior aspect of 1 implant neck, which was surrounded by pink-reddish tissue. All of the soft tissue around the implant was removed until the periosteum was reached. Histologic examination of the lamina propria revealed a cellular proliferation with imprecise boundaries, dense stromal component composed of spindle- to round-shaped mononucleated cells (fibroblasts and monocytes/macrophages), abundant multinucleated giant cells surrounding microscopic hemorrhagic foci, and deposits of hemosiderin; the diagnosis was peripheral giant-cell reparative granuloma (PGCG). Giant cells share the immunohistochemical expression of monocyte/macrophage markers (CD68, calprotectin [Mc387]) and osteoclastic cell markers (tartrate-resistant acid phosphatase, cathepsin K, and microphthalmia-associated transcription factor). After 6 months of follow-up, no bone resorption or recurrence of implant loss was observed. There have been only 12 case reports on dental implant-associated PGCG. Research results to date indicate that there may be little difference in immunophenotype among the giant cells of PGCG, central giant cell reparative granuloma, and peri-implant osteolysis. In conclusion, the immunohistochemical study confirms an osteoclast like giant cells phenotype differentiation in PGCG.