This study aimed to present and evaluate alternative lesion-specific mandibulectomy methods for preserving the mandibular anatomical structures as compared with the conventional virtual surgical plan. Fifteen patients who received segmental mandibulectomy were included in this study, and the following parameters were evaluated: (1) the disease-free bone margin, (2) the volume and surface between the tailor-made resection simulation and conventional resection simulation, and (3) the preserved mandibular anatomical structures. In all 15 patients, disease-free bone margins were confirmed by histopathology. Volumes of conventional resection simulation and tail-made resection simulation were 49,468.66 ± 14,007.96 mm 3 and 52,610.01 ± 13,755.33 mm 3 and the surfaces were 20,927.38 ± 4471.70 mm 2 and 22,356.49 ± 4185.73 mm 2 , respectively; these were statistically significant (both, p < 0.001). Mandibular dentition was partially preserved in six patients. Twelve of the 15 patients had changes in defect classification with preservation of the mandibular inferior border. In conclusion, alternative lesion-specific mandibulectomy was a less invasive method for effectively removing mandibular lesions while preserving the important anatomical structures of the mandible.