Bone regeneration procedures allow oral rehabilitation with dental implants also in edentulous ridges with severe bone atrophy. The integration of grafted materials with the host tissue can initiate regenerative, inflammatory and apoptotic response. Since molecular mechanisms exist at the basis of such response, the aim of this work is to investigate, by immunohistochemical analyses, the expression of proteins involved in the graft integration process, in parallel to clinical and histological modifications, occurring on sites treated with extraoral autologous bone graft deriving from the parietal region of the calvaria (eAB), intraoral autologous bone graft deriving from mandibular ramus (iAB) and heterologous bone graft from swine (hB) in human patients. In our study, the immunohistochemical expression of BSP, VEGF, eNOS in eAB samples was significantly higher (p < 0.05) compared to values recorded in iAB and hB samples. The inflammatory response, investigated by iNOS expression, was found lower in all autologous samples (eAB and iAB) compared to hB, at statistically significant values. Moreover, the expression of the pro-apoptotic molecule, Bax, resulted significantly lower (p < 0.05) in eAB than in iAB and hB samples. These values, together with the low number of apoptotic cells detected in autologous samples, suggest a good regenerative response when extraoral autologous bone graft is used in comparison to the response from the other grafts, and also suggest the use of calvaria graft as a predictable therapeutic procedure for repairing severe bone defects in oral and maxillofacial surgery, not only by clinical and biomechanical criteria, but also from a biomolecular aspect.