Ultraviolet (UV) radiation and the vitamin D system are involved in immunosuppression in the skin. Previous in vitro and animal studies suggest a role for mast cells in these mechanisms.To study vitamin D3 metabolizing enzymes, CYP27A1 and CYP27B1, in mast cells in epithelial skin cancers and psoriasis.Biopsies were collected from the non-lesional and lesional skin of patients with actinic keratosis (AK), Bowen's disease/squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and psoriasis. CYP27A1 and CYP27B1 in mast cells were analysed using a sequential double-staining method.The percentage of mast cells containing CYP27A1 was significantly higher in lesional than non-lesional skin in all diseases, especially in SCC and BCC. In addition, the percentage of mast cells containing CYP27B1 was significantly increased in BCC, AK, and psoriatic lesions as well. Interestingly, only about 5-6% and 2% of the mast cells expressed CYP27A1 and CYP27B1, respectively, in the non-lesional skin of psoriatic and AK patients. In contrast, 23-38% and 6-9% of the mast cells were immunopositive for CYP27A1 and CYP27B1, respectively, in the non-lesional skin of BCC and SCC patients. In human LAD2 mast cell cultures, about 30% and 15% of the mast cells showed CYP27A1 and CYP27B1, respectively, though the immunostainings of these enzymes were not markedly affected by UVB irradiation.Increased proportions of mast cells express vitamin D3 metabolizing enzymes in the lesional skin. Therefore, mast cells may promote an immunosuppressive environment, e.g., in skin carcinoma.