Patients with biotin deficiency present symptoms that are similar to those in patients with acrodermatitis enteropathica (inherent zinc deficiency). However, the association between biotin and zinc deficiency remains unknown. We have previously shown that epidermal keratinocytes of mice fed zinc-deficient (ZD) diets secreted more adenosine triphosphate (ATP) than those of mice fed zinc-adequate (ZA) diets and that epidermal Langerhans cells are absent in ZD mice. Langerhans cells highly express CD39, which potently hydrolyzes ATP into adenosine monophosphate (AMP). Thus, a lack of Langerhans cells in ZD mice leads to non-hydrolysis of ATP, thereby leading to the development of ATP-mediated irritant contact dermatitis. In this study, we examined if biotin-deficient (BD) mice showed the same underlying mechanisms as those in ZD mice. BD mice showed reduced serum zinc levels, disappearance of epidermal Langerhans cells, and enhanced ATP production in the skin. Consequently, irritant contact dermatitis was significantly enhanced and prolonged in BD mice. In conclusion, the findings of our study showed that biotin deficiency leads to zinc deficiency because of which patients with biotin deficiency show similar symptoms as those with acrodermatitis enteropathica.