BACKGROUND AND PURPOSE: The extensive application of advanced MR imaging techniques has undoubtedly improved our knowledge of the pathophysiology of amyotrophic lateral sclerosis. Nevertheless, the precise extent of neurodegeneration throughout the central nervous system is not fully understood. In the present study, we assessed the spatial distribution of cortical damage in amyotrophic lateral sclerosis by using a cortical thickness measurement approach. MATERIALS AND METHODS: Surface-based morphometry was performed on 20 patients with amyotrophic lateral sclerosis and 18 age- and sex-matched healthy control participants. Clinical scores of disability and disease progression were correlated with measures of cortical thickness. RESULTS: The patients with amyotrophic lateral sclerosis showed a significant cortical thinning in multiple motor and extramotor cortical areas when compared with healthy control participants. Gray matter loss was significantly related to disease disability in the left lateral orbitofrontal cortex (P = .04), to disease duration in the right premotor cortex (P = .007), and to disease progression rate in the left parahippocampal cortex (P = .03). CONCLUSIONS: Cortical thinning of the motor cortex might reflect upper motor neuron impairment, whereas the extramotor involvement seems to be related to disease disability, progression, and duration. The cortical pattern of neurodegeneration depicted resembles what has already been described in frontotemporal dementia, thereby providing further structural evidence of a continuum between amyotrophic lateral sclerosis and frontotemporal dementia.