The ability to step outside a routine—to select a new response over a habitual one—is a cardinal function of the frontal lobes. A large body of neuroimaging work now exists pointing to increased activation within the anterior cingulate when stimuli evoke competing responses (incongruent trials) relative to when responses converge (congruent trials). However, lesion evidence that the ACC is necessary in this situation is inconsistent. We hypothesized that this may be a consequence of different task procedures (context) used in lesion and neuroimaging studies. The present study attempted to reconcile the lesion and the fMRI findings by having subjects perform clinical and experimental versions of the Stroop task during BOLD fMRI acquisition. We examined the relationship of brain activation patterns, specifically within the anterior cingulate and left dorsolateral frontal regions, to congruent and incongruent trial types in different task presentations or contexts. The results confirmed our hypothesis that ACC activity is relatively specific to unblocked–uncued incongruent Stroop conditions that have not been used in large neuropsychological studies. Moreover, the size of the behavioral Stroop interference effect was significantly correlated with activity in ACC and left dorsolateral regions, although in different directions. The current results are discussed in terms of previous proposals for the functional roles of these regions in activating, monitoring, and task setting, and the relation of these findings to the disparate reports in recent case series is considered.