<i>Background:</i> Informant questionnaires may be useful in diagnosing early dementia. Conflicting results were found when these questionnaires were used to differentiate patients with mild cognitive impairment (MCI) from healthy elderly subjects. We evaluated the ability of the most commonly used informant questionnaire, the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), to discriminate between Alzheimer’s disease (AD), MCI and subjective memory complaints (SMC). <i>Methods:</i> Informants of 180 AD patients, 59 MCI patients and 89 SMC subjects who visited the Alzheimer Center of the VU University Medical Center between 2004 and 2007 completed the short Dutch version of the IQCODE. Logistic regression and receiver operating characteristic curves were used to evaluate the diagnostic ability of the IQCODE. <i>Results:</i> The IQCODE was able to differentiate AD from MCI and SMC, but was not able to differentiate SMC from MCI. <i>Conclusions:</i> The IQCODE may be helpful in diagnosing AD but is of limited use in differentiating MCI from SMC.