This case report describes a patient who developed the characteristic features of acute zonal occult outer retinopathy (AZOOR), but whose case was unusual because of macular involvement, recurrences, and association with an inflammatory CNS disorder. The patient was followed for > 7 years; clinical examinations, electroretinography, electro-oculography, cerebrospinal fluid evaluations, and magnetic resonance imaging (MRI) were used to document the recurrent AZOOR and CNS disorder. The patient first presented with entoptic symptoms and a scotoma referable to dysfunction of her peripapillary and peripheral right retina. At that time, she also had asymptomatic involvement of her peripheral left retina, cerebrospinal fluid pleocytosis, and multiple brain MRI signal abnormalities. During the next several years, she developed recurrences of AZOOR, which first affected her right macula and later involved her peripheral left retina. Visual electrophysiological studies confirmed impairment of outer retinal function. The patient developed her first neurological symptom, acute relapsing-remitting cervical myelitis, > 6 years after her visual presentation. Her clinical course, laboratory studies, and neurodiagnostic evaluations were consistent with CNS inflammation, but they were not typical of multiple sclerosis. Since AZOOR is a newly recognized disorder, its full clinical spectrum may not yet be established and could include CNS involvement.