Standardized neuropsychological test batteries demonstrate their greatest reliability and validity in patients with focal, well-defined neurologic disease. In these patients, the test profiles typically highlight focal areas of strengths and weaknesses in the brain. However, the clinical utility of standard test batteries and their reliance on scaled score differences is limited when evaluating patients with severe or diffuse neurobehavioral disorders. In the present case study, we applied the qualitative approach of Alexander Luria to the neuropsychological evaluation of a severely impaired adolescent, unable to complete psychometric tests. Luria's investigative method was able to assist in the localization of the brain dysfunction and the neurologic diagnosis of a young patient with an unusual neurologic presentation secondary to serious multisystem disease. The initial neuropsychological diagnostic impressions were later confirmed by diagnostic testing. The test results were also used to provide recommendations for ongoing neurorehabilitation of the patient.