Genetic factors have been shown to influence the risk of hand eczema, and may theoretically influence the frequency of eruptions as well as age at onset of the disease. However, the result may be confounded by atopic dermatitis, which is a major risk factor for development of hand eczema and is known to be influenced by genetic factors. In this study, the importance of genetic and environmental risk factors in the etiology of hand eczema, independent of atopic dermatitis, was investigated in a population-based twin cohort. In addition, any possible genetic influence on frequency of hand eczema eruptions and age at onset was explored. In all, 4,128 twin individuals (response rate 82%) answered a questionnaire on self-reported hand eczema. Similarity within twin pairs was estimated and quantitative genetic modelling performed. Controlling for age and atopic dermatitis, the effect of genetic risk factors was moderate and explained 41% of the variance in liability to develop hand eczema, leaving 59% of the variance to be caused by environmental factors. Genetic factors accounted for 31% of the variance in liability regarding frequency of eruptions. Environmental factors explained the variance in liability concerning age at onset.