Major depressive disorder (MDD) and frontotemporal dementia (FTD) are both disorders in elderly populations that involve the prefrontal cortex and appear to have similar neurocognitive deficits. This review examined whether there are testable deficits in cognition that are consistent across individuals within the same neuropathological condition that could be used to facilitate early diagnoses. Medline and PsychInfo databases were searched for cognitive studies of depressed and FTD patients that used a matched control group and reported findings with means and standard deviations (N = 312). Effect sizes for FTD patients with mild and moderately advanced disease were compared to effect sizes within subgroups of depressed patients, such as inpatients, outpatients and community volunteers. Moderately advanced FTD patients were more impaired than depressed patients over all domains, particularly in language ability, although depressed inpatients appeared similar to FTD patients in some domains. Effect sizes for FTD patients who were in the mild, or early, stage of the disease (MMSE = 28) were similar to those of depressed outpatients but slightly worse than those of community volunteers in all domains except semantic memory and executive ability. In the latter two domains, even mild FTD patients had notably large deficits. All FTD patients showed more severe deficits in some domains relative to other domains. In contrast, depressed patients tended to vary by clinical presentation or disease severity, but the magnitude of impairment for each subgroup remained relatively consistent across domains and they did not have the severe focal deficits in one or two domains demonstrated by FTD patients.