Background: The mediastinum is a vital sector of the thorax that contains vital intrathoracic structures such as the heart and great vessels, trachea and main bronchi, esophagus, thymus, venous and lymphatic structures, and nerve tissue. CT is the imaging modality of choice in diagnosis of mediastinal masses. The multiplanar capability of multidetector computed tomography (MDCT) is extremely helpful in delineating the full extent and source of vascularity thus helping in pre-operative planning of these patients. Objective: Detection of the role of multidetector CT in diagnosis and differentiation of mediastinal masses. Patients and methods: Forty patients were included in this study (20 females and 20 males), who presented with signs and symptoms suggestive for mediastinal masses. All patients were subjected to detailed history taking, clinical examination, laboratory studies, chest xray and MDCT examination. The correlation was done between the MDCT findings and the final diagnosis. The final diagnosis was made by operative procedures, CT guided biopsy, histopathological results and conservative management Results: Lymphoma was the commonest mediastinal mass forming 20% of cases , followed by neurogenic tumors (neuroblastoma, , neurofibroma , ganglioneuroma and schwannomatosis) forming about 17.5 % , then retrosternal thyroid (10%), teratoma (5%), thymoma (5%), metastatic lymphadenopathy (5%), esophageal carcinoma (5%), aortic aneurysm (5%), Bochdalek hernia (5%), hiatus hernia (5%), morgagni hernia (5%), esophageal achalasia (5%), esophageal leiomyoma (5%) and paraspinal abscess (2.5%). MDCT sensitivity was 92.86% & MDCT specificity was 100%. Conclusion: MDCT has a major and reliable role to play in the evaluation and assessment of the mediastinal masses; regarding the organ of origin, its density and mass effect upon adjacent structures, distribution pattern and extent of the lesion.