Background <p>Characterization of orbital masses is crucial in the therapeutic strategy planning owing to the fact that patient management greatly differs depending on the dignity of the orbital lesion. However, it is often difficult to differentiate malignant orbital masses from inflammatory pseudotumors (IPT) due to their comparable clinical presentation with proptosis in terms of the most common symptoms. Recently, magnetic resonance imaging (MRI) has become essential for the pre-treatment delineation of orbital tumors.</p> Aim of the study <p>To evaluate morphological, diffusion, and susceptibility perfusion criteria on MRI in terms of distinguishing orbital lymphoma from inflammatory pseudotumor.</p> Methods <p>Retrospective study of 58 patients retrieved from the available records of Alexandria University Hospital between August 2021 and August 2023, diagnosed with either lymphoma or inflammatory pseudotumor. I) Conventional MR protocol had been tailored to include the orbits and brain. The standard MR brain acquisition parameters were as follows: a) rapid scout images, b) multiplanar axial, coronal, sagittal T1- and T2-weighted (with and without STIR), c) diffusion-weighted imaging had been obtained using single-shot spin-echo echo-planar imaging in the axial plane, and d) dynamic T2* perfusion: Conventional post-contrast MRI fat-suppressed images are made in axial, sagittal and coronal planes, using the same parameters as non-contrast axial T1 images; then, subtraction is provided on axial images. Perfusion color map images are interpreted on a workstation.</p> Results <p>Results demonstrated a wide ADC range = 0.53–1.20 × 10⁻³&#xa0;mm²/s, with a mean value of 0.73. The lymphomas had an ADC range = 0.53–0.82 × 10⁻³&#xa0;mm²/s, and the mean value was 0.6482 × 10⁻³&#xa0;mm²/s. The IPTs had slightly higher ranges and values, showing an ADC range of 0.63–1.20 × 10⁻³&#xa0;cm²/s, and the mean ADC was 0.90 × 10⁻³&#xa0;mm²/s. ADC differences yielded a statistically significant difference (p &lt; 0.001*). Using a cutoff value of 0.82 × 10⁻³&#xa0;mm²/s yielded a sensitivity of 60%, 100% specificity, PPV = 100%, NPV = 62%, and accuracy of 76%. A more specific cutoff of &gt; 0.67 × 10⁻³&#xa0;mm²/s yielded a higher diagnostic achievement in terms of 100% specificity and 60% sensitivity, with an accuracy of 75.9%. Lymphomas showed a predominantly hyper-perfused pattern in susceptibility perfusion—seen in 21 lesions (= 91.3%), and only two (= 7.8%) showed iso-perfusion, and none of the lymphomas was hypo-perfused. On the contrary, inflammatory lesions were predominantly hypo-perfused (n = 31; 88.6%), 2 were iso-perfused (5.7%) and 2 were hyper-perfused (= 5.7%).</p> Conclusion <p>The combination of DWI and T2-weighted dynamic susceptibility contrast (DSC) perfusion can improve diagnostic performance in differentiating lymphoma from IPT, and is recommended to be used in an appropriate clinical setting.</p>