Studies with functional neuroimaging support the hypothesis of central pain augmentation in fibromyalgia syndrome (FMS) with functional differences in areas of the medial pain system. To clarify whether these findings are unique to patients with FMS, BOLD-signal patterns during and before tonic experimental pain were compared to healthy controls and patients with rheumatoid arthritis (RA) as a chronic pain disorder of somatic origin. We expected different BOLD-signal patterns in areas of the medial pain system that were most pronounced in patients with FMS. An fMRI-block design before, during and after an incision was performed in patients with FMS (n = 17), RA (n = 16) and in healthy controls (n = 17). A 2-factorial model of BOLD-signal changes was designed to explore significant differences of brain activation between the groups during the pain stimulus. Additionally, the correlation of brain activity during the anticipation of pain with the amount of the impending pain was determined. We observed a FMS-unique temporal brain activation of the frontal cortex in patients with FMS. Moreover, areas of the motor cortex and the cingulate cortex presented a FMS-specific relation between brain activity during pain anticipation and the magnitude of the subsequent pain experience. Our results support the hypothesis that central mechanisms of pain processing in the frontal cortex and cingulate cortex may play an important role in patients with FMS.