Abstract: Objective To compare the diagnostic accuracy of 99Tcm-MIBI SPECT/CT and 18F-FDG coincidence SPECT/CT for solitary pulmonary nodules. Methods A total of 88 cases suspected of solitary pulmonary nodules were analyzed retrospectively, of whom 36 were examined with 18F-FDG coincidence SPECT/CT and 52 with 99Tcm-MIBI SPECT/CT. The nature of the solitary pulmonary nodules (malignant or benign) were determined according to the pathological or follow-up (>2 years) results. The diagnostic accuracy of the two modalities for solitary pulmonary nodules was evaluated by ROC curve. The correlation of the lesion size and pathological grade determined by the two modalities with the L/N ratio was assessed using Spearman correlation analysis. Results 18F-FDG coincidence SPECT/CT and 99Tcm-MIBI SPECT/CT showed a similar area under curve (AUC) of the L/N ratio (0.92 vs 0.88, P=0.565) with diagnostic sensitivities of 76.92% (20/26) and 80.77% (21/26) and specificities of 100% (10/10) and 88.46% (23/26), respectively. For solitary pulmonary nodules with lesion diameter ≤2 cm, the AUC was 1.00 with 18F-FDG coincidence SPECT/CT and 0.90 with 99Tcm-MIBI SPECT/CT (P=0.746), while for nodules beyond 2 cm but below 3 cm, the AUCs were 0.79 and 0.89, respectively (P<0.001). In either of the two modalities, correlation analysis revealed no correlation of the L/N ratio with the pathological grade of the malignant lesions (P=0.771 and 0.077, respectively). The L/N ratio was not correlated with the size of the malignant lesion detected by 99Tcm-MIBI SPECT/CT (P=0.516) but was significantly correlated with the size of the malignant lesions detected by 18F-FDG coincidence SPECT/CT (P=0.016). Conclusion 99Tcm-MIBI SPECT/CT has a greater diagnostic accuracy than 18F-FDG coincidence SPECT/CT for solitary pulmonary nodules with lesion a diameter beyond 2 cm, and is therefore the primary choice for low-income patients.