Neuroimaging studies of human pain have revealed a widespread "pain matrix" distributed across both hemispheres of the brain. It is not resolved if the pain matrix is biased toward one hemisphere, although behavioral and clinical data suggest that pain is perceived differently on the two sides of the body, and several neuroimaging studies suggest that pain processing in some regions of cortex may be lateralized toward the right hemisphere. The current study used fMRI in nine subjects to determine if acute pain is preferentially processed in one cortical hemisphere. All cortical areas that were activated during the painful simulation were investigated, and several analytic approaches were used to directly compare activated regions to similar regions in the opposite hemisphere. Results indicated that four regions of the cortical pain matrix were activated either contralaterally (somatosensory cortex), or bilaterally (mid/posterior insula, anterior insula, and posterior cingulate). In addition, activation in five cortical regions during acute pain stimulation was localized either exclusively in the right hemisphere, or was strongly lateralized to the right. These five areas were in the middle frontal gyrus, anterior cingulate, inferior frontal gyrus, medial/superior frontal gyri, and inferior parietal lobule. The location of some of these regions is consistent with the idea that there may be a right-lateralized attentional system to alert an organism to an infrequent, but behaviorally relevant stimulus such as pain.