Voriconazole is a triazole antifungal agent approved to treat serious fungal infections. Although generally well tolerated, adverse effects include visual disturbances, gastrointestinal complaints, and cutaneous eruptions. Photosensitivity, pseudoporphyria, photoaging, and premature dermatoheliosis have been described. In this case series, Miller et al describe 5 melanoma in situ lesions arising in 2 patients undergoing long-term voriconazole treatment. The duration between therapy initiation and melanoma onset was short, and the clinically severe phototoxic effects and photodamage are clinically reminiscent of xeroderma pigmentosum. A better understanding of the pathophysiologic basis for voriconazole-associated phototoxic effects may provide valuable insight into the contribution of UV light to melanoma genesis.