Reconstruction of fractured, distorted, or missing parts in human skeleton presents an equal challenge in the fields of paleoanthropology, bioarcheology, forensics, and medicine. This is particularly important within the disciplines such as orthodontics and surgery, when dealing with mandibular defects due to tumors, developmental abnormalities, or trauma. In such cases, proper restorations of both form (for esthetic purposes) and function (restoration of articulation, occlusion, and mastication) are required. Several digital approaches based on three-dimensional (3D) digital modeling, computer-aided design (CAD)/computer-aided manufacturing techniques, and more recently geometric morphometric methods have been used to solve this problem. Nevertheless, comparisons among their outcomes are rarely provided. In this contribution, three methods for hemimandibular body reconstruction have been tested. Two bone defects were virtually simulated in a 3D digital model of a human hemimandible. Accordingly, 3D digital scaffolds were obtained using the mirror copy of the unaffected hemimandible (Method 1), the thin plate spline (TPS) interpolation (Method 2), and the combination between TPS and CAD techniques (Method 3). The mirror copy of the unaffected hemimandible does not provide a suitable solution for bone restoration. The combination between TPS interpolation and CAD techniques (Method 3) produces an almost perfect-fitting 3D digital model that can be used for biocompatible custom-made scaffolds generated by rapid prototyping technologies.