CT has rather low accuracy for the follow-up of tumors after therapy. This study was to determine whether the diagnostic accuracy can be improved with ^99mTc-HL91 SPECT in comparison with parallel results of CT imaging. Thirty patients of lung cancer or head & neck cancer, suspected of recurrences on clinical symptoms and CT during clinical follow-up after therapy, underwent ^99mTc-HL91 SPECT. The radioactivity ratios of tumor to normal tissues (T/NT) were calculated using the region of interest technique. Results of ^99mTc-HL91 SPECT were verified by histopathology. The ^99mTc-HL91 average uptake ratios of T/NT in the group of recurrent lesions and non-recurrent lesions were 1.58±0.16 and 1.18±0.14, respectively. A significant difference was found between T/NT data of the two phases (t=4.87, P<0.001).The^99mTc-HL91 SPECT shows sensitivity of 72.73%, specificity of 89.47% and accuracy of 83.83% for differentiating recurrent lesion, while the CT shows sensitivity of 63.63%, specificity of 84.21% and accuracy of 76.67%. A combination of ^99mTc-HL91 SPECT and CT for 21 patients with lung cancers or head & neck cancers with congruent results shows sensitivity of 100%, specificity of 94.12% and accuracy of 95.23%. It is concluded that ^99mTc-HL91 SPECT may play a role in differentiating recurrent lesions in patients with lung cancer and head & neck cancer. Furthermore, the combination of CT and ^99mTc-HL91 SPECT is a more effective method for diagnosing recurrence of lung cancer and head & neck cancer.