Background: 99mTc-Sestamibi (MIBI) thyroid scintigraphy is an increasingly used non-invasive imaging tool for evaluation of thyroid nodules. Yet the results are heterogeneous. The aim of this study was to evaluate the utility of 99mTc-MIBI for differentiating benign from malignant thyroid nodules with a cytological reading of follicular neoplasm. Patients and Methods: Twenty-one patients were prospectively imaged by 99mTc-Pertechnetate and MIBI scans with addition of SPECT/CT. Images were visually interpreted using a scoring system: 0; no, 1; faint, 2; isointense and 3; intense uptake. Pattern of tracer washout in delayed images was compared to early images; decreased, constant or increased uptake. Quantitative analysis was done to calculate washout and retention indices for planar (WOI-P and RI-P) and SPECT/CT images (WOI-S and RI-S). Inter-reader agreement was conducted for visual analysis. Histopathology and radiologic follow up were used as the gold standard. Results: Sixteen and 5 nodules proved benign and malignant respectively. The majority of nodules (63%) were hypofunctioning. Delayed MIBI scan scoring proved superior to the early one with 100% NPV. Pattern of washout in SPECT/CT images had significantly higher specificity, PPV, NPV, and accuracy than that of the planar images (P=0.003), yet both had the same sensitivity (80 %). I-P had a significant AUC of 0.850 (P= 0.021) and a cut-off value of ≥ -114 gives 100% sensitivity and specificity, additionally it was the only the significant predictor factor for malignancy (P=0.02). Inter-observer kappa agreement was excellent for early planar and delayed SPECT/CT (95%CI: 0.00-0.133, p < 0.01 and 95%CI: 1.00-1.00, p < 0.0 respectively). Conclusion: The visual scoring system yields a high sensitivity and NPV, yet it has a low specificity. Addition of SPECT/CT improves the diagnostic accuracy of the washout pattern in the delayed images. RI-P was the only significant predictor factor for malignancy.