In the jaws, the healing process of bone defects occurs differently compared with other anatomical sites where healing is done by the formation of scar tissue. This is due to physiological bone remodeling and continuous bone resorption and apposition. In the case of large cysts, there is an increased risk of postoperative infection due to the retraction of the blood clot on the bony walls. The use of plasma rich in growth factors (PRGF), with or without autologous bone addition, for filling the cystic cavities is beneficial not only for its antimicrobial effect, but also due to simultaneously release of growth factors from platelet alpha granules and adhesive proteins. The aim of our work was to emphasize the spontaneous bone healing of the maxilla and mandible after the enucleation of large and medium-sized cysts in asymptomatic patients of different age. The outcome of three patients who underwent surgery for removal of radicular cysts is presented. Imagistic [cone-beam computed tomography (CBCT)] and histological examination was performed aiming to evaluate the quality of new bone at the site of the bone defect, after different time intervals. By using PRGF approach, the healing of mandibular bone occurred 18 months after cystectomy in a smoker patient, 54-year-old, while the healing of maxillary bone using autologous bone mixed with PRGF occurred after six months in a 63-year-old patient. In a young patient (14 years old), the regeneration period was six months, using PRGF and a fibrin cloth for filling the defect.