Leuprolide acetate is a gonadotropin-releasing hormone agonist (GnRHa) that is used in the treatment of various neoplastic diseases, such as advanced prostate cancer, breast cancer, endometriosis, and leiomyoma. Furthermore, treatment with GnRHa, including leuprolide acetate, has been the standard of care for central precocious puberty for more than 20 years. Leuprolide has relatively less side effects on the skin. The most common reported dermatologic side effect is subcutaneous granuloma at the site of injection. Generalized papular eruption evoked by leuprolide acetate has been rarely reported. A 15-year-old girl with precocious puberty was referred to our department with a 4-day history of pruritic papular eruption on whole body. Histopathologic findings showed vacuolar alteration of the basal cell layer, papillary dermal edema, and lymphohistiocytic perivascular infiltration with some eosinophils in the upper dermis, which heightened the suspicion of a drug reaction. She ceased leuprolide acetate and started corticosteroid treatment. Following the treatment, her skin lesions were markedly improved. We herein report an unusual case of generalized papular eruption caused by leuprolide acetate.