Background: Orbital apex syndrome (OAS) can be caused by a broad range of disorders. There are several challenges present in the evaluation of these patients and in reaching a final diagnosis. We report the case of a 69-year-old male who presented with OAS that was determined to be secondary to a rare malignancy (NK cell lymphoma, nasal type). Methods: We analyze the pitfalls and diagnostic delays in this patient’s evaluation. Furthermore we propose a work up for undifferentiated cases of OAS. Results: To accurately diagnose the underlying cause of OAS, a direct biopsy should be obtained whenever possible. The appropriate imaging sequences should be arranged as lesions in this region can be easily missed. Adjunct tests include assessment in the serum and CSF for granulomatous and infectious diseases, along with chest imaging. As many causes are PET enhancing, PET CT is a useful modality for identifying sites for biopsy. Conclusions: OAS can provide a diagnostic challenge for clinicians, however a systematic approach can help determine the underlying etiology.