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Late-life depression is frequently associated with cognitive impairment. Because of the overlap of symptoms, however, it can be challenging to discern a neurocognitive disorder (NCD) from a late-life depressive disorder. Although neuropsychological testing provides evidence, there are limited neurochemical or neuroimaging biomarkers for the etiological classification of NCD versus late-life depression. Without formal DSM-5 criteria for a dementia syndrome of depression (DSD), patients may be incorrectly diagnosed as having an NCD. Without recognition and appropriate aggressive treatment, patients may develop severe depression with cognitive impairment leading to significant morbidity. It is crucial that clinicians become aware of and assess for elements that differentiate DSD from neurocognitive disorders. In so doing, this syndrome can be identified and treated early in its course, allowing for the best patient outcomes. In this article, the authors demonstrate, through a case presentation, the diagnostic challenges and clinical value of accurately identifying and treating DSD.