Introduction: The introduction of Multi-Detector Computed Tomography (MDCT) has revolutionised clinical practice. Mediastinal lesions represent challenging problems faced by the radiologist and often a chest radiograph is inadequate for answering the queries of clinicians. MDCT is employed to diagnose various causes of mediastinal widening and often correct diagnosis is obtained using CT alone, thus obviating invasive diagnostic procedures. Aim: To assess the diagnostic accuracy of MDCT in mediastinal mass lesions compared to histopathology. Materials and Methods: A prospective observational study comprised of 52 patients who underwent MDCT examination for evaluation of mediastinal masses. All these patients subsequently underwent histopathological examination either by CT-guided biopsy, transthoracic needle aspiration, endoscopic biopsy or by surgical resection. Sensitivity, specificity and accuracy of each type of lesion was calculated and tabulated. Results: The study population comprised of 52 patients out of whom 43 cases (83%) were predicted correctly by CT when compared with histopathology diagnosis. The sensitivity of detecting malignancy was 100% and specificity was 92.6%. The present study had accuracy of 96.2% in differentiating malignant mediastinal masses from benign lesions. Conclusion: MDCT is useful in evaluating the distribution of mediastinal masses and their relationship to adjacent structures and differentiating between malignant mediastinal masses from benign lesions.