Theoretical models and empirical work indicate a critical role of the NAcc in salience processing. For instance, the NAcc not only responds to appetitive and aversive information, but it also signals novelty, contextual deviance, and action monitoring. However, because most studies have investigated only one specific type of salience independently, it remains unclear how the NAcc concurrently differentiates between different forms of salience. To investigate this issue, we used intracranial electroencephalography in human epilepsy patients together with a previously established visual oddball paradigm. Here, three different oddball categories (novel, neutral, and target images) were infrequently presented among a standard scene image, and subjects responded to the target via button press. This task allowed us to differentiate “item novelty” (new vs neutral oddballs) from “contextual deviance” (neutral oddballs vs standard images) and “targetness” (target vs neutral oddballs). Time-frequency analysis revealed a dissociation between item novelty and contextual deviance on the basis of decreases in either θ (4–8 Hz) or β power (20–30 Hz). Targetness, on the other hand, was signaled by positive deflections in the stimulus-locked local field potentials, which, importantly, correlated with subjects' reaction times. These findings indicate that, in an ongoing stream of information, the NAcc differentiates between types of salience by distinct neural mechanisms to guide goal-directed behavior.