The purpose of this study was to compare Tc(99m) MIBI SPECT imaging with computed tomography (CT) for assessment of post-radiotherapy treatment response in pharyngeal carcinoma. Twenty-two subjects took part in this study, which included six patients with nasopharyngeal carcinoma (Group I), three patients with oropharyngeal carcinoma and eight patients with hypopharyngeal carcinoma (Group II), and five control patients (Group III). All scans were analyzed qualitatively and quantitatively and correlated with findings on local examination and biopsy. Various indices such as ratios of nasopharynx, oropharynx, and hypopharynx to scalp (NSR, OSR, HSR), to nuchal muscles (NNR, ONR, HNR), and parotid glands (NPR, OPR, HPR) were calculated. The mean values of these above mentioned ratios calculated in the control group (Group III) were used as cutoff values to determine the presence or absence of tumor tissue in the patient groups (Groups I and II). The cutoff values calculated were 2.89 (NSR), 1.39 (NNR), 0.57(NPR), 3.83 (OSR), 1.81 (ONR), 0.83 (OPR), 2.86 (HSR), 1.73 (HNR), and 0.59 (HPR). The results revealed 100% sensitivity for primary nasopharyngeal tumors but less sensitivity for primary oropharyngeal and hypopharyngeal tumors (63.6%). Based on a relative decrease in tracer uptake, Tc(99m) MIBI SPECT scan was able to predict partial remission, complete remission, and no response on post-therapy scans. There were three false-negative results of disease progression in addition to evidence of disease eradication on CT scan. Thus Tc(99m) MIBI SPECT imaging has shown promising results in the detection of primary tumors and evaluation of treatment response much earlier than CT scan, which needs further exploration and large-scale studies.