Using diffuse optical tomography (DOT), we detected activation in the somatosensory cortex and frontal brain areas following tactile (brush) and noxious heat stimulation. Healthy volunteers received stimulation to the dorsum of the right hand. In the somatosensory cortex area, tactile stimulation produced a robust, contralateral to the stimulus, hemodynamic response with a weaker activation on the ipsilateral side. For the same region, noxious thermal stimuli produced bilateral activation of similar intensity that had a prolonged activation with a double peak similar to results that have been reported with functional MRI. Bilateral activation was observed in the frontal areas, oxyhemoglobin changes were positive for brush stimulation while they were initially negative (contralateral) for heat stimulation. These results suggest that based on the temporal and spatial characteristics of the response in the sensory cortex, it is possible to discern painful from mechanical stimulation using DOT. Such ability might have potential applications in a clinical setting in which pain needs to be assessed objectively (e.g., analgesic efficacy, pain responses during surgery).