Background: Keloids are a common lesion arising from sites of previous trauma and are a considerable source of morbidity because of continued growth of lesions, pruritus, and physical appearance. They consist of mesenchymal cells embedded in a stroma of disordered collagen matrix. Clinically, keloids are distinguished from scars in that keloids demonstrate continued growth over the borders of the original injury. Keloids appear with increased frequency in patients of African and Asian descent. Currently, no entirely satisfactory method of treatment exists for these lesions. Recently, a patient who was enrolled in a clinical trial of topical tacrolimus for atopic dermatitis applied this drug to a keloid and noted clearing. Objective: Based on this clinical observation and the observation that rapamycin, a chemically similar compound to tacrolimus, is known to inhibit signaling from the gli-1 oncogene, we examined keloids and scars for expression of Gli-1 protein. Methods: Skin sections from keloids and scars were examined by immunohistochemical staining for gli-1. To further confirm the presence of gli-1 expression in keloids, reverse transcriptase-polymerase chain reaction was carried out. Results: Expression of gli-1 was strongly elevated in keloids compared with scars. Conclusion: These results provide a rationale for the treatment of keloids with topical rapamycin analogs, including tacrolimus. Clinical trials of topical tacrolimus are warranted. (J Am Acad Dermatol 2001;45:707-11.)