Intramedullary cord hyperintensity at T2-weighted MRI is a common imaging feature of disease in the spinal cord, but it is nonspecific. Radiologists play a valuable role in helping narrow the differential diagnosis by integrating patient history and laboratory test results with key imaging characteristics. The authors present an algorithmic approach to evaluating intrinsic abnormality of spinal cord signal intensity (SI), which incorporates clinical evaluation results, time of onset (acute vs nonacute), cord expansion, and pattern of T2 SI abnormality. This diagnostic approach provides a practical framework to aid both trainees and practicing radiologists in workup of myelopathy.©RSNA, 2019.