Distinct patterns of activity within the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (dlPFC) reported in neuroimaging studies during tasks involving conflict between competing responses have often been cited as evidence for their key contributions to conflict-monitoring and behavioral adaptation, respectively. However, supporting evidence from neuropsychological patients has been scarce and contradictory. We administered a well-studied analog of the Wisconsin Card Sorting Test, designed to elicit conflict between 2 abstract rules, to a cohort of 6 patients with damage to ACC or dlPFC. Patients who had sustained more significant damage to the ACC were not impaired either on a measure of “conflict cost” nor on measures of “conflict-induced behavioral adaptation.” In contrast, damage to dlPFC did not affect the conflict cost measure but abolished the patients’ ability to adapt their behavior following exposure to conflict, compared with controls. This pattern of results complements the findings from nonhuman primates with more circumscribed lesions to ACC or dlPFC on the same task and provides converging evidence that ACC is not necessary for performance when conflict is elicited between 2 abstract rules, whereas dlPFC plays a fundamental role in behavioral adaptation.