Background: Benign cystic mesothelioma, a tumor characteristically found in women during the reproductive years, is rare after bilateral oophorectomy or menopause, suggesting hormonal sensitivity. Case: We treated a 17-year-old woman with a rapidly increasing and symptomatic benign cystic mesothelioma with a long-acting GnRH agonist. A rapid and continued reduction in volume corresponded to the induction and maintenance of a hypoestrogenic state over a 6-month period. However, the subsequent addition of a combination of estrogen and progestin (known as add-back therapy) resulted in a gradual increase in cyst volume, which progressed after discontinuation of all therapy. Resumption of GnRH-analog therapy alone reduced cyst volume again, and the patient underwent surgical removal. Conclusion: Long-acting GnRH agonists may have a role in the conservative management of these rare neoplasms. The reduction in volume concomitant with a hypoestrogenic state and regrowth with addition of add-back therapy further suggest extreme sensitivity of this tumor to one or both hormones.