OBJECTIVE: To determine the value of 201-thallium (201-Tl) and technetium-99m sestamibi (Tc-99m MIBI) single photon emission computed tomography (SPECT) for detecting primary undifferentiated carcinoma of nasopharyngeal type (UCNT), residual/recurrent tissue, and lymph node involvement. STUDY DESIGN AND SETTING: SPECT of head and neck was prospectively performed in 46 patients with a history of, UCNT (201-Tl in 24 patients, Tc-99m MIBI in 22). CT/MRI findings. clinical follow-up, and pathohistological verification served as a gold standard for calculating sensitivity, specificity, and accuracy of each scintigraphic technique. Tumor-to-background index (T/Bg) was derived when SPECT findings were positive. RESULTS: Sensitivity of 201-Tl SPECT was 87 percent, with 78 percent specificity. 83 percent accuracy, and T/Bg of 4.05 +/- 1.50. Tc-99m MIBI SPECT had 85 percent sensitivity, 78 percent specificity, 82 percent accuracy. and T/Bg of 4.45 +/- 1.27. CONCLUSION AND SIGNIFICANCE: 201-Tl SPECT and Tc-99m MIBI SPECT are useful for detecting primary UCNT, residual/recurrent disease. and lymph node involvement. This use is particularly valuable after chemoradiotherapy when CT/MRI may be ambiguous. (c) 2007 American Academy of Otolarynlgololgy-Head and Neck Surgery Foundation. All rights reserved.