The dermatology life questionnaire index (DLQI) and the Skindex are the most commonly used dermatology-specific health-related quality of life (HRQOL) instruments. Although these tools are used in international surveys and clinical trials, the cross-cultural equivalence of their items has not been documented. We used differential item functioning (DIF), which is part of the Rasch model, to assess the impact of cultural background on the items of the DLQI and Skindex-29 and-17. The data of the 450 psoriasis patients, who attended in- and outpatient dermatology centers, was collected retrospectively from five European and one US center. The DLQI and Skindex-29 scales did not fit the Rasch model (P<0.0008) and 10/10 of the DLQI and 19/29 of the Skindex-29 items displayed significant DIF. Although the psychosocial scale of the Skindex-17 fitted the Rasch model, half or more of the items of the psychosocial (6/12) and the symptom scale (4/5) showed significant DIF across countries. These findings suggest that psoriasis patients from different countries respond differently to a substantial proportion of DLQI and Skindex items despite having the same level of underlying HRQOL impairment. Therefore, these instruments should not be used in their current form in international studies.