The aim of this study was to replicate, in patients with multiple sclerosis (MS), the three-cluster cognitive-behavioral classification proposed by Turk and Rudy. Sixty-two patients attending a tertiary MS rehabilitation center completed the Pain Impact Rating questionnaire measuring activity interference, pain intensity, social support, and emotional distress. The General Health Questionnaire-28 and the Multiple Sclerosis Impact Scale-29 assessed disability and restriction in participation. Cluster analysis classified patients into three cognitive-behavioral groups (40.4%, "adaptive copers"; 36.5%, "dysfunctional"; and 23.1%, "interpersonally distressed"). Patients in groups with higher levels of activity interference, emotional distress due to pain, and lower perceived levels of social support had significantly higher levels of depression on the General Health Questionnaire-28 (P less than 0.003), and reported a greater impact on their physical and psychological functioning (P less than 0.001) on Multiple Sclerosis Impact Scale-29 subscales. Possible cut-points were identified to aid clinicians in classifying patients into clusters for individualized treatment. More research is needed to improve the understanding of pain and the potential use of cognitive-behavioral clusters in patients with MS. These may be useful in the development of tailored early intervention, which may reduce pain-related disability and contribute to patient's overall well being.