Mistletoe preparations standardised to the content of mistletoe lectin are supposed to improve quality of life (QoL) in patients with cancer. To obtain a validated and sensitive research instrument, the Life Quality Lectin-53 (LQL-53) Questionnaire was developed in three phases: item generation via interviews with 42 patients, item selection by means of a study with 109 cancer patients, and psychometric testing. The LQL-53 includes 46 items assigned to the subscales General well-being, Emotional well-being, Vitality Hope, Locus of control, Social relationships'', and Physical complaints, plus seven items dealing with possible adverse effects of mistletoe treatment. Psychometric testing was carried out in a study with 112 patients with solid tumours who were treated with a mistletoe preparation standardised to mistletoe lectins for 12 weeks. Internal consistency (Cronbach''s ) was between 0.72 and 0.94. Test–retest reliability was r of 0.72. Subscales correlated highly with external criteria. Construct validity, as determined by Multitrait Scaling Analysis, resulted in an optimal assignment of items to subscales (scaling success) for four of the subscales. During the course of the therapy, significant improvement in QoL was found in all subscales. In two of the subscales, effect size was high (>0.80), and in five other subscales it varied between 0.53 and 0.78.