OBJECTIVE Patients with chronic low back pain (cLBP) show a range of behavioral patterns that do not correlate with degree of spinal abnormality found in clinical, radiological, neurophysiological, or laboratory investigations. This may indicate an augmented central pain response, consistent with factors that mediate and maintain psychological distress in this group. METHODS Twenty-four cLBP patients were scanned with functional magnetic resonance imaging while receiving noxious thermal stimulation to the right hand. Patients were clinically assessed into those with significant pain-related illness behavior (Waddell signs [WS]-H) or without (WS-L) based on WS. RESULTS Our findings revealed a significant increase in brain activity in WS-H versus WS-L patients in response to noxious heat in the right amygdala/parahippocampal gyrus and ventrolateral prefrontal and insular cortex (at a VoxelPThreshold = 0.01). We found no difference between groups for heat pain thresholds (t(22) = -1.17, p = .28) or sensory-discriminative pain regions. CONCLUSIONS Patients with cLBP displaying major pain behavior have increased activity in the emotional circuitry of the brain. This study is the first to suggest an association between a specific clinical test in cLBP and neurobiology of the brain. Functional magnetic resonance imaging may provide a tool capable of enhancing diagnostic accuracy and affecting treatment decisions in cases where no structural cause can be identified.