Acanthosis nigricans (AN) is a skin condition associated with hyperinsulinemia and insulin resistance and has been shown to be a risk factor for type 2 diabetes. The influence of genetic factors on AN and the basis of its association with type 2 diabetes and its risk factors are unknown. Using data from 397 participants from two Mexican American family studies, we investigated the heritability of AN and its genetic correlation with other diabetes risk factors. AN was examined as both a continuous trait and a dichotomous trait by means of a previously described validated scale. The results indicated that the heritability (h2) for AN, when examined as a continuous trait, was high (0.58+/-0.10) and statistically significant (P<0.001). The h2 for AN as a dichotomous trait was estimated to be moderate (0.23+/-0.05) and was also significant (P=0.018). The additive genetic correlations between AN (either as a continuous trait or a dichotomous trait) and type 2 diabetes and its risk factors, including body mass index and fasting insulin, were high or moderately high and statistically significant. The random environmental correlations, by contrast, were low and statistically insignificant. These data suggest that genes that influence AN have pleiotropic effects on diabetes and its risk factors.