Owing to overlapping symptomatology, differentiating between late-life depression (LLD) and Alzheimer’s Disease (AD), is clinically challenging. Amyloid PET may be used to improve AD diagnosis, however it is expensive and not widely available. Here we apply a two-step MRI driven approach exploiting the different degree of hippocampal volume loss that is present in both disorders to derive hippocampal volume thresholds for identifying patients who could be diagnosed without a PET exam. Using the more cost-effective hippocampal volumetry approach, we could correctly classify half of the patient sample. This increased to 90% when adding 18F-flutametamol PET for the remaining patients.