The EORTC QLQ-C30 health-related quality of life (HRQoL) questionnaire was developed for use in clinical cancer trials. It has also been applied in studies of patients with chronic nonmalignant pain in spite of nondocumented validity. Validation of the EORTC QLQ-C30 in this patient population and comparison with the traditional first choice HRQoL instrument in chronic nonmalignant pain, the SF-36, are, therefore, required. Two hundred eighty-six patients admitted to the tertiary multidisciplinary pain center at St. Olavs University Hospital in Trondheim, Norway, completed both the EORTC QLQ-C30 and the SF-36 at admittance. Correlations between EORTC QLQ-C30 and SF-36 measures of the same concept were between 0.70 and 0.81 for all five domains covered by both instruments. Internal consistency was below 0.70 for the EORTC QLQ-C30 scales physical functioning (0.57), pain (0.68), role functioning (0.43), cognitive functioning (0.66), and nausea/vomiting (0.53), as well as the SF-36 scale role emotional functioning (0.66). Large floor or ceiling effects were seen for several EORTC QLQ-C30 scales. While SF-36 addresses no other symptoms than pain and fatigue, the EORTC QLQ-C30 also includes sleep, financial difficulties, nausea/vomiting, dyspnea, appetite loss, constipation, and diarrhea. Even though some EORTC QLQ-C30 scales have unsatisfactory internal consistency, EORTC QLQ-C30, similar to SF-36, has overall acceptable psychometric properties. The EORTC QLQ-C30 is a valid alternative to the SF-36 when a broader assessment of symptoms is desired.