Objective To investigate MRI diagnosis and differential diagnosis spinal epidural lymphoma and leukemia. Methods The medical records of patients with spinal epidural lymphomas (15 cases) and leukemia (10 cases) who admitted to the hospital from March 2016 to March 2018 were analyzed retrospectively. All cases received MR examination and analyze the location and MRI findings of spinal epidural lymphoma and leukemia. Results Of the 25 patients, 23 (92.00%) had diffuse lesions of the spine and its appendages, and most of them were spinal epidural lymphomas. Patients with thoracic segment and intraspinal epidural lesions were the most. MRI findings showed that spinal epidural lymphomas mostly occurred in the spinal canal and outside spinal canal, while leukemia mainly occurred in the spinal canal (P<0.05). Spinal epidural lymphomas mainly occurred in the thoracic vertebrae, while leukemia mainly occurred in the thoracic vertebrae, lumbosacral vertebrae and pelvis (P<0.05). MRI findings showed diffuse spotted and patchy short T2 signal on sagittal T1WI and T2WI of spinal epidural lymphomas, and semilunar and half-moon-shaped equal T1 and equal T2 signal on cross-sectional T1WI and T2WI of epidural soft tissues. However, such findings were not found in patients with leukemia (P<0.05). Conclusion MRI findings of spinal epidural lymphoma and leukemia are characteristic, which is of certain reference value for diagnosis of the disease.