High percentages (35-78%) of resected mandibles without bone invasion have been reported in squamous cell carcinoma (SCC), adjacent or fixed to the mandible, stressing the need for accurate imaging methods. The aim of this study is to determine the value of bone single photon emission computed tomography (SPECT) for the evaluation of mandibular invasion by SCC. Seventy-nine patients with SCC, adjacent or fixed to the mandible, were included. The results of bone SPECT were compared to the histology of the resection specimens. Bone SPECT was positive in all 50 patients with mandibular invasion and negative in 17 of 29 patients without mandibular invasion. In conclusion, a negative bone SPECT rules out mandibular invasion. Important clinical implications are then that further imaging is not necessary and that the resection can be kept limited. Inclusion of SPECT in the preoperative assessment of these patients will lead to a considerable reduction of unnecessary mandibular resections.