PURPOSE: The aim of this study was to evaluate the performance of a novel flat-panel single photon emission computed tomography (SPECT)/CT in patients with suspicion of osteomyelitis (OM) of the jaw in comparison with conventional orthopantomography (OPT), planar bone scintigraphy (PS) and CT alone. METHODS: Forty-two patients (21 female, 21 male, mean age 52, range 10-84 years) with suspected OM (n = 38) or exacerbation of a known OM (n = 4) were investigated with OPT, CT alone, PS and combined SPECT/CT. Images were separately reviewed by a nuclear physician/radiologist and jaw surgeon regarding presence of OM. Additionally, the different methods were rated regarding their usefulness for diagnosis (5-point scale: from 1 = diagnostic to 5 = useless). Biopsy served as the standard of reference in 30 patients and clinical/imaging follow-up of at least 6 months in 12 patients. RESULTS: In 35 of 42 patients the final diagnosis of OM was established according to the reference standard. Sensitivity, specificity and accuracy for OPT was 59, 100 and 66 %, for CT alone 77, 86 and 79 %, for PS 100, 71 and 95 % and for SPECT/CT 100, 86 and 98 %. SPECT/CT was significantly more accurate compared with CT alone (p = 0.0078) and OPT (p = 0.001). SPECT/CT was rated as the most useful imaging modality (mean value 1.2) compared with PS (2.2), CT (2.5) and OPT (3.2). CONCLUSION: SPECT/CT is an accurate method to assess the presence of OM of the jaw and superior to CT alone and OPT. SPECT/CT slightly improved the specificity of PS. However, SPECT/CT in this study was not significantly more accurate compared with PS and whether the advantages to the patient of a one-stop study as opposed to doing separate CT and PS justifies its routine use in terms of cost requires further study.