We present the case of a 61-year-old man who underwent I-123 metaiodobenzylguanidine (MIBG) scintigraphy based on clinical suspicion of pheochromocytoma. The study was nondiagnostic secondary to diffuse muscle uptake. On review of his medications, the patient was found to be taking mirtazapine, a tetracyclic antidepressant (Remeron). We hypothesize that the MIBG biodistribution was altered by mirtazapine-mediated blockade of the presynaptic alpha-2 receptor. To our knowledge, tetracyclic antidepressants have not been previously reported to cause altered biodistribution on I-123 MIBG scans.