OBJECTIVES: To validate the PRISM (Pictorial Representation of Illness and Self Measure) tool, a novel visual instrument, for the assessment of health-related quality of life in dermatological inpatients compared with the Dermatology Life Quality Index (DLQI) and the Skindex-29 questionnaires and to report qualitative information on PRISM. DESIGN: In an open longitudinal study, PRISM and Skindex-29 and DLQI questionnaires were completed and HRQOL measurements compared. SETTING: Academic dermatological inpatient ward. PARTICIPANTS: The study population comprised 227 sequential dermatological inpatients on admission. INTERVENTION: Patients completed the PRISM tool and the Skindex-29 and DLQI questionnaires at admission and discharge. MAIN OUTCOME MEASURES: PRISM Self-Illness Separation (SIS) score; Skindex-29 and DLQI scores; and qualitative PRISM information by Mayring inductive qualitative context analysis. RESULTS: The PRISM scores correlated well with those from the Skindex-29 (rho = 0.426; P < .001) and DLQI (rho = 0.304; P < .001) questionnaires. Between PRISM and Skindex-29 scores, the highest correlations were for dermatitis (rho = 0.614) and leg ulcer (rho = 0.554), and between PRISM and DLQI scores, the highest correlations were for psoriasis (rho = 0.418) and tumor (rho = 0.399). The PRISM tool showed comparable or higher sensitivity than quality of life questionnaires to assess changes in the burden of suffering during hospitalization. Inductive qualitative context analysis revealed impairment of adjustment and self-image as major aspects. Patients overall expected symptomatic and functional improvement. In patients with psoriasis and leg ulcers, many expected no treatment benefit. CONCLUSIONS: The PRISM tool proved to be convenient and reliable for health-related quality of life assessment, applicable for a wide range of skin diseases, and correlated with DLQI and Skindex-29 scores. With the PRISM tool, free-text answers allow for the assessment of individual information and potentially customized therapeutic approaches.