Objectives: The purpose of this study is to present 2 clinical case studies in which large herniated disks were not detected on magnetic resonance imaging (MRI), leading to false negative results, and discuss some issues regarding potential shortcomings of MRI. Clinical features: Cases of cervical and lumbar herniated nucleus pulposus (HNP) are presented. Each patient had severe pain and neurological deficit. The patients had positive physical examination findings suggestive of HNP despite the negative MRI scans. Both subsequently underwent myelography and computed tomography to arrive at the final and definitive diagnosis of HNP. Intervention and outcome: Both patients failed a course of conservative care that included manual and mechanical traction, manual mobilization, myofascial release techniques, epidural steroid injections, oral steroid and narcotic medications, and rehabilitative exercises. Both patients eventually required surgical decompression. Conclusion: False negative MRI results in these cases of large HNPs emphasize the importance of case history and physical examination findings as the basis for ordering diagnostic tests. The conclusion of this article is simple; no single diagnostic test should be considered as 100% accurate, as false negative studies may occur that may mislead the patient and clinician.