Most of musculoskeletal diseases involve pain and reduced physical functioning. Recognition of the coexistence of more than one musculoskeletal disease is important because they are relatively common and has a substantial impact on health-related quality of life (HRQoL). Our aim was to compare the results of four generic QoL questionnaires--QoL-5, Nottingham Health Profile (NHP), Short Form (SF)-6D, and Visual Analogue Scale (VAS)--in five different patient groups. Two hundred and one patients representing five different disease groups (knee osteoarthritis, osteoporosis, back pain, rheumatoid arthritis and ankylosing spondylitis), randomly selected through the Ankara Numune Education and Research Hospital Physical Medicine and Rehabilitation Outpatient Clinic, were included in the study. Scores indicating low QoL for each of the five diseases compared are reported. Patients in each disease group stated high disability. No strong correlation between any of the scales could be determined, and NHP was identified as the only scale able to differentiate between the diseases. Many instruments are available for measuring HRQoL. The QoL-5, NHP, SF-6D, and VAS are four commonly used generic (i.e., not disease-specific) measures for quantifying HRQoL in patients with musculoskeletal disorders. Most studies have focused on only one musculoskeletal disease, but comorbidity of musculoskeletal disorders is common. We emphasize in this study the effect of multiple musculoskeletal diseases on HRQoL.