Objective: To investigate the capacity of the Pain Belief Screening Instrument (PBSI) to discriminate between subgroups for targeting of treatment, investigate effects of treatment tailored to patients' individual and functional goals, and identify a suitable treatment dosage for patients with low risk of disability. Explorative study, Part I. Design: Randomized, controlled clinical trial with four treatment conditions. Methods: Patients in primary healthcare (n=45) with musculoskeletal pain for ≥4 weeks were included. PBSI-identified subgroups were validated by comparing scores on four established instruments. Measures of disability and patients' ratings of global outcome were used to examine treatment effect. Results: PBSI data adequately defined patients with either high or low risk of disability. Patients in the tailored treatment rated global outcome as better than in the non-tailored treatment. No differences were found on disability measures. For the low-risk group, the brief tailored treatment was as effective as the non-targeted control treatment. Conclusion: The PBSI adequately defined subgroups. Tailored treatment was partially superior to physical exercise treatment. Targeting by treatment dosage was effective for low-risk patients but remains to be investigated for high-risk patients. Treatment integrity for tailored treatments was compromised and is to be further explored in the following study.