Short but accurate cognitive screening instruments are required in busy clinical practice. Although widely-used, the diagnostic accuracy of the standardised Mini-Mental State Examination (SMMSE) in different dementia subtypes remains poorly characterised. We compared the SMMSE to the Quick Mild Cognitive Impairment (Qmci) screen in patients (n = 3020) pooled from three memory clinic databases in Canada including those with mild cognitive impairment (MCI) and Alzheimer’s, vascular, mixed, frontotemporal, Lewy Body and Parkinson’s dementia, with and without co-morbid depression. Caregivers (n = 875) without cognitive symptoms were included as normal controls. The median age of patients was 77 (Interquartile = ±9) years. Both instruments accurately differentiated cognitive impairment (MCI or dementia) from controls. The SMMSE most accurately differentiated Alzheimer’s (AUC 0.94) and Lewy Body dementia (AUC 0.94) and least accurately identified MCI (AUC 0.73), vascular (AUC 0.74), and Parkinson’s dementia (AUC 0.81). The Qmci had statistically similar or greater accuracy in distinguishing all dementia subtypes but particularly MCI (AUC 0.85). Co-morbid depression affected accuracy in those with MCI. The SMMSE and Qmci have good-excellent accuracy in established dementia. The SMMSE is less suitable in MCI, vascular and Parkinson’s dementia, where alternatives including the Qmci screen may be used. The influence of co-morbid depression on scores merits further investigation.