Skin toxicity due to voriconazole is well recognized. Recently, several series have reported skin cancer, particularly cutaneous squamous cell carcinoma (C-SCC), following photosensitivity reactions among patients receiving long-term voriconazole (>12 months). Almost all patients were immunosuppressed, including stem cell and solid organ transplant recipients. A case-control study of lung transplant recipients identified long-term voriconazole (median cumulative dose: 76 grams) and residence in areas of strong sun exposure as independent risk factors for C-SCC. The mechanism(s) by which voriconazole may predispose to skin cancer is not clear. Moreover, the relative contribution of voriconazole and other factors such as immunosuppression, ultraviolet exposure, advanced age and skin type is unknown. Until further data are available, voriconazole should be used carefully for durations >6-9 months, particularly among patients with risk factors for skin cancer. In patients requiring prolonged voriconazole, diligent skin examinations, avoidance of excess sunlight, and liberal use of UV protectants are advisable.