Hand eczema is a disease of long duration, affecting the individual and society. The purpose of this study of 100 patients (51 females and 49 males) at an occupational dermatology clinic was to investigate whether the generic questionnaire Short Form-36 (SF-36), and the dermatology-specific Dermatology Life Quality Index (DLQI) are appropriate for assessing health-related quality of life (HRQL) in patients with hand eczema, and whether gender differences in HRQL could be detected. HRQL was affected by hand eczema, measured with both SF-36 and DLQI. The SF-36 showed more impaired HRQL for females than for males, in the mental health dimension, whereas no gender-related differences were detected with the DLQI. To compare the instruments we used factor analysis, with a polychoric correlation matrix as input, thus taking the ordinal aspect of the data into account. There was a high correlation between the instruments for physical health, but lower for mental health. In this context our interpretation of the factor analysis is that the SF-36 measures mental health better than the DLQI. The SF-36 therefore appears suitable for use in future studies for measuring HRQL, and gender differences in HRQL, in persons with reported hand eczema.