Recent findings have established that epidermal Langerhans cells (LCs) promote polyaromatic hydrocarbon (PAH)-induced carcinogenesis independent of their immunological properties by generating mutagenic PAH metabolites. In this issue, Girardi and colleagues (2014) extend their previous work and demonstrate that this mutagenic metabolism of LCs is indeed mediated by preferential expression of the cytochrome P450 enzyme CYP1B1, but that LCs cells exert their pro-carcinogenic effects also independently of CYP1B1.