BACKGROUND Radioisotope methods have shown to be useful in the non-invasive diagnosis of thyroid nodules over the past years. The present prospective study aims to evaluate the efficacy of gamma imaging using single and dual tracer using Tc-99m pertechnetate and Tc-99m tetrofosmin for evaluation and management of thyroid nodules. METHODS Dynamic (perfusion) imaging was performed after injecting 148-185 MBq (4-5 mCi) of Tc-99m pertechnetate followed by static imaging. A second, dynamic (perfusion) imaging study within same week was performed with 296-370MBq (8-10mCi) of Tc-99m tetrofosmin on same group of patients followed by early and delayed images. Results of radionuclide perfusion scan from both studies were compared qualitatively with postsurgical histopathology or fine needle aspiration cytology (FNAC). RESULTS Total 65 nodules in 50 patients were included in the study. With single tracer, the specificity and accuracy of Tc-99m pertechnetate was 23% and 45% and for Tc-99m tetrofosmin scan was 40% and 49%. When dual tracers were evaluated for the same group of patients, the specificity was 56% and accuracy was 55%. CONCLUSIONS Dual Tracer technique with Tc-99m pertechnetate and Tc-99m tetrofosmin could be helpful in selecting nodules need surgical intervention. This technique can be used for convenient and rapid diagnostic evaluation of thyroid nodules non-invasively. We suggest a combination of fine needle aspiration biopsy and dual use of Tc-99m-pertechnetate and Tc-99m-tetrofosmin as a routine diagnostic approach to thyroid nodules.