The impact of Behçet's disease on higher cognitive functions is still poorly understood. We proposed (1) to characterize the neuropsychological profile of Behçet's disease patients with (Neuro-BD) and without (BD) neurological manifestations; (2) to identify which clinical, psychopathological, and genetic variables are related to neuropsychological performance; and (3) to explore the association between cognitive functioning and neuroimaging findings in BD patients. Fifteen Neuro-BD and 35 BD patients in the nonactive phase of their illness underwent a neurological examination, performed a comprehensive battery of neuropsychological tests, and answered the hospital anxiety and depression scale. Human leukocyte antigen (HLA)-B*51 genotyping was also performed. Patients' neuropsychological performances were compared to those of healthy demographically matched subjects. Within one month from the testing date, a subset of 20-BD patients underwent a magnetic resonance imaging (MRI) scan. Fifty-three percent of Neuro-BD and 40% of BD patients were impaired at least on one neuropsychological measure (i.e., digit span-forward). Poorer cognitive functioning in Neuro-BD was associated with parenchymal involvement, whereas in BD it was related to presence of white matter changes in the frontal lobes, history of headache complaints, or higher levels of anxiety and depression. Current prednisone intake had a positive impact on neuropsychological performance. Disease duration, time since onset of neurological manifestations, or presence of HLA-B*51 allele had no significant influence. Our results indicate that Behçet's disease may affect cognitive abilities in the absence of overt neurological symptoms. These findings point to an insidious course of neurological involvement.