The neural origins of the cortical response to rare sensory events remain poorly understood. Using simultaneous event-related potentials and magnetic resonance imaging, we investigated the anatomical profile of regional activity at various processing stages during performance of auditory and visual variants of an oddball paradigm. The earliest rarity-detection response was found in sensory-specific cortices, rapidly spreading to tertiary association areas, mesial temporal and frontal cortices by 150-200 ms. P3m-related activity was not found in sensory-specific cortices. On the basis of the anatomic distribution of P3m-related activity, this component is likely to reflect more generalized cognitive abilities hosted by association cortical regions.