A correct clinical diagnosis in the early stage of Alzheimer disease is not only of importance given the current available treatment with acetylcholine esterase inhibitors, but would be the basis for disease-modifying therapy slowing down or arresting the degenerative process. Moreover, in the last years, several efforts have been made to determine if a patient with mild cognitive impairment has incipient Alzheimer disease, i.e. will progress to Alzheimer disease with dementia, or have a benign form of mild cognitive impairment. In this review, the recent published reports regarding progress in early and preclinical Alzheimer disease diagnosis are discussed and the role of peripheral and cerebrospinal fluid biomarkers highlighted. Approaches combining panels of different biomarkers show promise for discovering profiles that are characteristic of Alzheimer disease, even in the pre-symptomatic stage. More work is needed but available novel perspectives offered by recent introduced technologies shed some lights in identifying incipient Alzheimer disease in mild cognitive impairment subjects.