OBJECTIVE To compare neoplastic and nonneoplastic disease in the anterior extradural space (AES) with regard to the contour of the disease and the tethering of the central septum, as seen on axial magnetic resonance (MR) images. METHODS In this institutional review board-approved HIPAA-compliant study, the data of patients who had AES disease determined at MR imaging and underwent diagnostic biopsy were studied. Two blinded observers reviewed the MR images and assigned the patients to one of two groups on the basis of the contour of AES disease: those with a centrally convex disease contour posteriorly and those whose disease contour was tethered in the midline to the posterior aspect of the vertebral body. Biopsy results served as the standard of reference. The two-tailed Fisher exact test, the Breslow-Day test, and κ statistics were used to compare groups. The sensitivity, specificity, and accuracy of the midline tethered contour of AES disease for the detection of neoplasm were calculated. RESULTS The data of 32 patients (16 men, 16 women; mean age, 68 years) were studied. Seventeen patients had malignant epidural disease. Fifteen patients had nonneoplastic epidural disease: Six patients had hematomas, and nine had abscesses. A greater proportion of AES neoplasms (13 [76%] and 14 [82%] of 17 lesions for observers 1 and 2, respectively) than nonneoplastic AES lesions (four [27%] and three [20%] of 15 lesions for observers 1 and 2, respectively) demonstrated midline tethering of the central septum. For observers 1 and 2, a unilobed or bilobed appearance of AES disease had sensitivities of 76% (13 of 17 lesions) and 82% (14 of 17 lesions), respectively; specificities of 73% (11 of 15 lesions) and 80% (12 of 15 lesions), respectively; and accuracies of 75% (24 of 32 lesions) and 81% (26 of 32 lesions), respectively, for the detection of neoplasm. The mean κ value for interobserver variability was 0.62 (95% confidence interval: 0.35, 0.90). CONCLUSIONS AES disease preserving the midline tethering of the central septum is more common with neoplastic disease than with infections or hematomas.