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Objective: To determine the diagnostic accuracy of Diffusion-Weighted Imaging (DWI) and Apparent Diffusion Coefficient (ADC) mapping in differentiating benign from malignant thyroid nodules by taking histopathology as the gold standard., Study Design: Across-sectional analytical study., Place and Duration of Study: Department of Radiology at Combined Military Hospital (CMH), Lahore, from August 2012 to July 2013., Methodology: Thirty-five patients, who were referred to radiology department of CMH, Lahore, for ultrasound or Fine Needle Aspiration Cytology (FNAC) of thyroid gland, fulfilling the inclusion and exclusion criteria, were included in the study. They were evaluated on 1.5 Tesla MRI machine with T1- and T2-weighted imaging as well as fat-suppressed technique. DWI was done using b-values of 0 and 1000 s/mm2and ADC values were calculated for the thyroid nodules. All of these patients were subjected to ultrasound guided core biopsy and histopathology results were correlated with ADC values., Results: The benign nodules showed facilitated diffusion while malignant nodules showed restricted diffusion. T-test was used to assess the difference in mean ADC values between benign and malignant nodules. The mean ADC value of the malignant thyroid nodules (0.94 ±0.16 x 10-3mm2/s) was significantly lower than that of the benign thyroid nodules (1.93 ±0.13 x 10-3mm2/s) (p-value < 0.05). ADC value of 1.6 x 10-3mm2/s was used as a cut-off, for differentiating benign from malignant thyroid nodules. The sensitivity, specificity, PPV, NPV and diagnostic accuracy of DWI and ADC values in differentiating benign from malignant thyroid nodules were 93%, 95%, 93%, 95% and 92.3%, respectively., Conclusion: DWI is a non-invasive diagnostic tool for characterization and differentiation between benign and malignant thyroid nodules. It not only decreases the burden of unnecessary surgeries when pre-operative FNAC and biopsy are inconclusive, but is also helpful in reaching a definite diagnosis when a nodule is not amendable to biopsy due to any reason.