The present study was conducted to cross-validate and extend the hypothesis that olfactory dysfunction could discriminate between groups of patients with Alzheimer's disease and major depression. Forty patients meeting the DSM-IV criteria for either Alzheimer's disease or major depression (20 per group) underwent assessment with the Pocket Smell Test (PST), a three-item screening measure of odor identification, and the Mini-Mental State Examination (MMSE). A PST score of < or = 1 (1 or 0 correct) discriminated between the groups with a hit rate of 97.5% (sensitivity = 95%, specificity = 100%). The optimal hit rate for the MMSE (< or =24) was less effective (hit rate = 90%, sensitivity = 80%, specificity = 100%). Age, gender, and education had minimal impact on the PST for both groups. Olfactory assessment continues to add to the diagnostic utility in the differential diagnosis of Alzheimer's disease versus major depression in elderly patients.