Primary lateral sclerosis (PLS) has been defined as rare, and the neuropsychological changes remain poorly defined. We studied 20 patients with a diagnosis of PLS. We carried out an extensive psychometric testing including a general assessment (memory, language, attention, visual-constructional ability and praxis) and a more specific assessment of prefrontal and premotor cortex functions in order to characterize the neuropsychological profile of the patients compared to matched controls, and explore executive functions and premotor cortex functions. None of the PLS patients was demented but they all presented memory deficits reflecting an executive dysfunction. All patients but three had signs of premotor and/or prefrontal cortex deficits. The cognitive impairment in PLS, specifically related to a frontal lobe dysfunction, seems qualitatively similar to ALS. Our results suggest a patchy distribution of cortical involvement in PLS but it remains difficult to draw any definite conclusion as to the spatio-temporal progression of the disease into the different regions of the frontal lobe.