Background: Lymphoma is a kind of blood cancer that begins in lymphocytes, white blood cells that are part of the lymphatic system. The lymphatic system is part of the immune system and helps fight infection. This study's objective was to detect role of diffusion MRI in the algorithm of diagnosis of mediastinal lymphoma and assessment of post therapeutic response. Methods: Cross sectional study was conducted to patients with mediastinal lymphoma diagnosed by CT and biopsy and admitted in Benha university Hospital from 1st November 2022 to 31th September 2023 (10 months). Results: ROC analysis was done for ADC to distinguish between Hodgkin and non-Hodgkin lymphoma patients. It revealed a significant AUC of 0.828 (P = 0.003), with a 95% confidence interval ranging from 0.661 – 0.995. The best cutoff point was ≤0.887, at which sensitivity, specificity, PPV, and NPV were 63.6%, 100%, 100%, and 82.6%, respectively. For ADC to distinguish between Hodgkin and non-Hodgkin lymphoma in mediastinal masses, It revealed a significant AUC of 0.875 (P = 0.02), with a 95% confidence interval ranging from 0.671 - 1. The best cutoff point was ≤ 0.887, at which sensitivity, specificity, PPV, and NPV were 75%, 100%, 100%, and 75%, respectively. For ADC to predict treatment response, It revealed a significant AUC of 0.894 (P < 0.001), with a 95% confidence interval ranging from 0.762 – 1.0. The best cutoff point was> 1.165, at which sensitivity, specificity, PPV, and NPV were 91.7%, 88.9%, 84.6%, and 94.1%,