Background: Dementia must be diagnosed accurately and early in the disease course to allow pathology-specific treatments to be effective. Dementia with Lewy bodies (DLB) is often misdiagnosed as Alzheimer’s disease (AD), especially at the prodromal stage. Objective: To compare the clinical and neuropsychological profiles of Mild Cognitive Impairment (MCI) patients who, at follow-up, progressed to AD (retrospectively AD-MCI) or DLB (retrospectively DLB-MCI) or remained MCI. Methods: This longitudinal study used an unselected sample from a memory clinic database. A total of 1,848 new patients were seen at the memory clinic between 1994–2015. Of these, 560 patients (30%) had an initial diagnosis of MCI and were considered for the study. Inclusion criteria were patients who had a diagnosis of MCI at initial assessment and a minimum of 12 months’ follow-up. Results: Of the 429 MCI patients with follow-up data, 164 (38%) remained MCI, 107 (25%) progressed to AD, and 21 (5%) progressed to DLB. The remainder progressed to alternative diagnoses. At baseline, DLB-MCI patients performed significantly worse on visuospatial function and letter fluency tests than both AD-MCI and stable-MCI groups, and better on episodic memory tests than the AD-MCI group. At baseline, DLB-MCI patients had a significantly higher mean UPDRS score and were more likely to have REM sleep behavior disorder and fluctuating cognition. Conclusion: DLB-MCI patients have a specific cognitive and neuropsychiatric profile which should alert clinicians to the possibility of prodromal DLB. This is relevant when considered in the context of early disease-specific therapy.