It has been proposed that at least two distinct processes are engaged during task-switching: reconfiguration of the currently relevant task-set and interference resolution arising from the competing task-set. Whereas in healthy individuals the two are difficult to disentangle, their disruption is thought to cause different impairments in brain-damaged patients. Yet, the observed deficits are inconsistent across studies and do not allow drawing conclusions regarding their independence. Forty-one brain tumor patients were tested on a task-switching paradigm. We compared their performance between switch and repeat trials (switch cost) to assess rule reconfiguration, and between trials requiring the same response (congruent) and a different response for the two tasks (incongruent) to assess interference control. In line with previous studies, we found the greatest proportion of errors on incongruent trials, suggesting an interference control impairment. However, a closer look at the distribution of errors between two task rules revealed a rule perseveration impairment: Patients with high error rate on incongruent trials often applied only one task rule throughout the task and less frequently switched to the alternative one. Multivariate lesion-symptom mapping analysis unveiled the relationship between lesions localized in left orbitofrontal and posterior subcortical regions and perseveration scores, measured as absolute difference in accuracy between two task rules. This finding points to a more severe task-setting impairment, not reflected as a mere switching deficit, but instead as a difficulty in creating multiple stable task representations, in line with recent accounts of OFC functions suggesting its critical role in representing task states.