A 5-year-old girl with DeSanctis-Cacchione syndrome (a severe variant of xeroderma pigmentosum) was referred for evaluation of multiple eyelid and bulbar conjunctival squamous cell carcinomas. Examination evidenced multiple vegetating lesions on the eyelid, bulbar conjunctiva, and cornea of both eyes. As the lesions were considered not to be manageable by surgical excision and would have required exenteration, photodynamic therapy was performed on the patient's left eye. Three months after photodynamic therapy, the patient presented with a dramatic increase in the extension of the tumors. Since xeroderma pigmentosum is a DNA repair disorder, the radiation involved in photodynamic therapy probably played an iatrogenic role in the evolution of the case. We believe that photodynamic therapy may be harmful to patients with DNA repair disorders.