The diagnostic accuracy of technetium-99m methoxyisobutylisonitrile (Tc-MIBI) single photon emission computed tomography (SPECT) of head and neck to differentiate between recurrent or residual nasopharyngeal carcinomas (NPC) and benign lesions after radiotherapy was evaluated, and compared with computed tomography (CT). Thirty-six NPC patients 4 months after radiotherapy underwent Tc-MIBI SPECT and CT of head and neck, as well as histopathological examination of nasopharyngeal biopsies. Based on the biopsy results, the sensitivity, specificity, and accuracy of CT were 73%, 88%, and 83%, respectively. The sensitivity, specificity, and accuracy of Tc-MIBI SPECT were 64%, 96%, and 86%, respectively. The sensitivity, specificity, and accuracy of combined Tc-MIBI SPECT and CT were 100%, 88%, and 92%, respectively. Tc-MIBI SPECT had a better specificity and a lower sensitivity to differentiate benign lesions from recurrent/residual NPC when compared with CT The combined use of CT and Tc-MIBI SPECT significantly increased accuracy compared with the single use of either Tc-MIBI SPECT or CT to differentiate benign lesions recurrent/residual NPC.