Cognitive impairment is common in elderly people and represents clinical feature of neurodegenerative diseases. Not all of patients with Mild Cognitive Impairment (MCI) finally develop dementia and it is interesting to investigate the role of possible markers for early diagnosis. Hyperhomocysteinemia is associated to several pathologies including cognitive impairment; aim of this study is to evaluate the correlation between cognitive performance assessment and homocysteine plasma levels. Total 74 patients and 75 healthy controls were enrolled and MCI were defined by a MMSE score lower than 26 after adjustment for years of schooling. Homocysteine plasma levels were determined. Homocysteine levels significantly raised in patients with cognitive impairment and showed a significant negative association with MMSE score. Finally, our data show that a moderate risk of cognitive impairment could be associated to high homocysteine plasma levels.