In response to recent publications from pain neuroimaging experiments, there has been a debate about the existence of a primary pain region in the brain. Yet, there are few meta-analyses providing assessments of the minimum cerebral denominators of pain. Here, we used a statistical meta-analysis method, called activation likelihood estimation, to define (1) core brain regions activated by pain per se, irrelevant of pain modality, paradigm, or participants and (2) activation likelihood estimation commonalities and differences between patients with chronic pain and healthy individuals. A subtraction analysis of 138 independent data sets revealed that the minimum denominator for activation across pain modalities and paradigms included the right insula, secondary sensory cortex, and right anterior cingulate cortex (ACC). Common activations for healthy subjects and patients with pain alike included the thalamus, ACC, insula, and cerebellum. A comparative analysis revealed that healthy individuals were more likely to activate the cingulum, thalamus, and insula. Our results point toward the central role of the insular cortex and ACC in pain processing, irrelevant of modality, body part, or clinical experience; thus, furthering the importance of ACC and insular activation as key regions for the human experience of pain.