Our ability to perceive changes in the sensory inputs is critical for survival. We investigated the change detection system in the human brain using magnetoencephalography. This system constantly compares the incoming sensory inputs with those received earlier and establishes a “regularity” in the stimuli received. The activation of this system does not simply depend on the stimulus itself, but rather on the deviance of the incoming signal from that received in the immediate past. We demonstrated that the secondary somatosensory cortex (SII) and superior temporal gyrus (STG) in the somatosensory and auditory systems, respectively, were involved in change detection. Responses in SII and STG were enhanced by a larger magnitude of change, regardless of the intensity of the physical stimulus, and by a longer duration of the preceding stimuli that contributed to the previously established sensory regularity. We speculate that activation of the change detection system reflects an individual’s sensitivity to change and is related to their psychological characteristics for pain perception.