Few cases or peri-implant peripheral giant cell lesions (PGCL) have been reported in the literature. The aim of this study was to report 13 new cases of peri-implant PGCL and compare the expression of smooth muscle actin, Bcl-2 protein, GLUT-1, CD68, osteoprotegerin, receptor activator of nuclear factor kappa-B, Ki-67 and CD34 in these cases with PGCL and central giant cell lesions (CGCL). Clinical data were retrieved from the laboratory records and histological analysis was performed using HE-stained slides. Immunohistochemical reactions for the above mentioned antibodies were performed and digitally scored. Peri-implant PGCL mostly affected the posterior mandible of adult females. CD68 and Bcl-2 expressions were higher in conventional PGCL and CGCL than in peri-implant PGCL (p=0.033 for CD68 and p<.0001 for Bcl-2). Microvessel density was higher in conventional peripheral than in central and peri-implant PGCL (p=0.002). Proliferative index of the mononuclear cells showed no statistically significant differences comparing the three groups but it was higher in peri-implant PGCL. The current study demonstrated that peri-implant PGCL is more common in the posterior mandible of adult females. There were some differences in microvessel density, proliferative activity and expression of CD68 and Bcl-2 among conventional PGCL, peri-implant and CGCL. Further studies are encouraged to better understand these early findings.