The early differentiation between Alzheimer's disease (AD) and frontal variant of frontotemporal dementia (fvFTD) is frequently difficult, albeit critical for the adequate management of patients and their caregivers. In order to assess the accuracy of CSF levels of beta-amyloid 1-42 (Aβ), tau (τ) and Thr 181-phosphorilated tau (Pτ) in the early differentiation of AD from fvFTD, we designed a prospective study in which patients have been followed up for at least 2 years. Seventy-two patients with AD and 42 patients with fvFTD showed significantly different CSF levels of Pτ (increased in AD, p = 0.0001), Aβ (reduced in AD, p = 0.03), and ratios of Pτ to Aβ (p = 0.003). ROC analyses showed that the ratio Pτ/Αβ is able to predict diagnosis with an AUC of 0.73 (optimal level being 0.16) corresponding to a sensitivity of 80% and a specificity of 68%. Our findings suggest that CSF metabolites may be the important tools in the early differential diagnosis between AD and fvFTD, albeit to be correlated with clinical, neuropsychological and bio imaging features.