To date no investigation has proven accurate and reliable for assessing mandibular invasion by carcinoma prior to surgery. This prospective study compared a new imaging modality, single photon emission computed tomography (SPECT), with clinical examination and high resolution CT scanning to evaluate the sensitivity and specificity of each method in detecting mandibular invasion by squamous cell carcinoma. Twenty-nine patients (21 men, 8 women) with an oral cavity/oropharyngeal carcinoma were studied. All underwent primary surgery and/or radiotherapy where indicated. Resected mandibles were decalcified and examined for tumour infiltration. Imaging studies were read independently by two experienced observers. Clinical examination predicted bone invasion with a sensitivity of 90% and a specificity of only 25%. CT had a sensitivity of 89% and a specificity of 57% while SPECT imaging had a sensitivity of 100% and a specificity of 29%. Using Fisher's exact test and the Kappa statistic for pairwise comparisons between each method, SPECT imaging was complementary to CT in the pre-operative assessment of mandibular invasion.