Objectives: 1) Assess various rapid methods for processing mandible bone margins for histopathologic examination. 2) Determine the optimal method for intraoperative use. Methods: Multiple bone samples were collected from a fresh (<12 hours post-mortem) human cadaveric mandible using a standard 3mm core bone biopsy trocar. The cored specimens were placed 30 minutes in 10% formalin (transport time) and then for 15-75 minutes in 1 of 3 decalcifying solutions (Decal A, Calex, EDTA Decal). Controls were placed in 10% formalin. After each designated decalcification time period, specimens were cryosectioned or paraffin-embedded and reviewed by a head and neck surgical pathologist blinded to the treatment groups. The specimens were assessed for overall quality, adequacy of decalcification, soft tissue quality, marrow quality, and presence of artifact. Results: Bone margin specimens collected with a 3mm core bone biopsy trocar and processed with all 3 decalcifying solutions for 15 minutes yielded acceptable quality and sufficient decalcification for histopathologic assessment. In addition, the trabecular, intact soft tissue and marrow were well-preserved with good cellular architecture. Conclusions: Mandible bone margins can be rapidly processed for histologic evaluation using cored specimens with only 15 minutes of decalcification, allowing for intraoperative assessment of a bone margin. A prospective clinical trial of patients with cancer invasion in the mandibular bone to confirm cancer cells are identifiable with this rapid processing method is planned.