To evaluate the usefulness of 99mTc-tetrofosmin (TF) SPECT in the detection of intrathoracic malignant lesions, we studied 304 patients, 261 with malignant and 43 with benign lesions; 196 of the former had non-treated primary tumors, 193 lung cancer (LC) and 3 mesotheliomas, 11 had LC recurrences and 54 had metastases from different kinds of tumors. Twenty-nine patients with primary tumors were re-checked after chemotherapy or surgery. In all patients, after 740 MBq TF injection, both planar and SPECT images were acquired and analysed qualitatively, SPECT images also semiquantitatively. Scintigraphy was always compared to CT. SPECT showed higher sensitivity, specificity and accuracy values than CT (98.1, 90.7 and 97 vs. 96.2, 81.4, and 93.9%, respectively), their combined use achieving 100% sensitivity and 98.8% accuracy. Planar did not give more information than SPECT, showing a significantly lower sensitivity (63.2%) and accuracy (67.4%). SPECT showed higher accuracy values than CT and planar (86.9 vs. 78.3 and 69.6%) in NSCLC mediastinal lymph node staging. Moreover, SPECT was concordant with CT in correctly evaluating the response to chemotherapy or surgery in all monitorized primary tumors cases, except in one in whom only SPECT detected residual tumor. The semiquantitative analysis added useful information in differentiating malignant from benign lesions and in monitoring the response to chemo-therapy. TF SPECT appears a highly accurate diagnostic method in the detection of intrathoracic malignant lesions, in lungs and pleura, as well as in NSCLC mediastinal lymph node staging and in monitoring treatment effectiveness, playing a complementary role to CT in selected cases.