The aim of this study is to determine the contribution of neck and chest 99mTc-pertechnetate scan to the management of postoperative patients with suspicious metastatic differentiated thyroid cancer (DTC), particularly to the prediction of response to radioiodine (131I) therapy. Just before 131I administration, a total of 184 postoperative DTC patients with stimulated serum thyroglobulin (ssTg) >10 ng/mL were enrolled to undergo neck and chest 99mTc-pertechnetate scan, which were directly compared with post-therapeutic 131I scan to determine the concordance of site and number of metastatic lesions. The percentage changes in ssTg between 99mTc-pertechnetate-avid group and 99mTc-pertechnetate-nonavid group were compared, and the response to 131I in both groups was analyzed according to the nature of 99mTc-pertechnetate avidity as well. The percentages of concordance between 99mTc-pertechnetate and 131I scan in detecting metastases were 65.7% and 26.0% in per-patient and per-site analyses with low unweighted kappa, respectively. 99mTc-pertechnetate scan led to a change in therapeutic decision making in 19/184 (10.3%) patients. In 72 patients with 131I-avid metastases, the ssTg in 99mTc-pertechnetate-avid group (n = 13) decreased significantly compared with that in 99mTc-pertechnetate-nonavid group (n = 59) (median: −81.56% vs −48.14%; Z = −4.276, P = .000). The difference of therapeutic response between 99mTc-pertechnetate-avid group and 99mTc-pertechnetate-nonavid group was statistically significant (χ2 = 8.4; P = .03). Although the consistency between 99mTc-pertechnetate scan before 131I administration and post-therapy 131I scan in detecting metastases is low, identifying metastases in postoperative DTC patients with elevated ssTg via 99mTc-pertechnetate scan prior to 131I therapy provides incremental value for therapeutic decision making. Notably, patients with 99mTc-pertechnetate-avid metastases may be more prone to benefit from 131I therapy than those with 99mTc-pertechnetate-nonavid metastases.