We report a case of pathology-proven acute disseminated encephalomyelitis (ADEM) in which the patient’s symptoms were solely cognitive. Although cognitive dysfunction is a well-recognized symptom in adults with multiple sclerosis, cognitive assessment of adults with ADEM has rarely been reported. A 35-year-old woman was referred to our center for evaluation of cognitive disturbance and demyelinating lesions seen on brain magnetic resonance imaging (MRI). We performed a neurologic examination, full neuropsychological assessment, brain MRI, blood and cerebrospinal fluid analyses, visual evoked potentials, and brain biopsy. The patient’s Mini-Mental State Examination score was 26/30. Cognitive assessment revealed multiple severe dysfunctions, mainly in executive and attention tasks. She scored below the normal range on the Digit Span Forward and Backward Test and the Trail Making Test Part B. The Frontal Assessment Battery showed deficits in mental flexibility, motor programming, and inhibitory control. She also scored in the impaired range on tests of verbal fluency and memory. The brain MRI and biopsy confirmed a diagnosis of ADEM. This case report points to the limitations of relying on clinical presentation, neuroimaging, and current controversial diagnostic criteria in diagnosing ADEM in adults, and highlights the essential role of pathologic evaluation.