The usefulness of the Mini-Mental State Examination (MMSE) as a screening test for identifying cognitive impairment in patients with multiple sclerosis (MS) has been questioned because many patients who score above the suggested cutoff score of 24 exhibit severe focal or global cognitive deficits. We reevaluated the usefulness of the MMSE by studying 85 patients with clinically definite MS who also received an extensive battery of neuropsychological tests. Although scores on the MMSE were negatively correlated with the number of neuropsychological tests on which patients with MS displayed impairment, the MMSE was not sufficiently sensitive to identify precisely defined dementia in these patients. The MMSE was nonetheless a useful predictor of focal cognitive impairment, particularly in relapsing-remitting patients with relatively minor physical disabilities. Additional analyses suggested strategies for minor modifications of the MMSE that may improve its sensitivity and specificity for identifying dementia while preserving its major advantages as a screening examination: brevity and ease of administration and scoring.