Leuprorelin is a luteinizing hormone-releasing hormone (LH-RH) agonist that is used as an agent of androgen deprivation in some patients with prostate cancer. When administered in depot form, local granulomatous reactions may occur at the injection site, which may mimic masses and which are associated with treatment failure. We present a patient who, over a period of 5 years, developed multiple intramuscular gluteal masses while receiving leuprorelin therapy via intramuscular depot injections; biopsy of one of the masses showed the specific histologic features of leuprorelin granuloma. To our knowledge, this entity has not been described in the radiology literature. Awareness of this entity is necessary to suggest the correct diagnosis in patients with a history of leuprorelin depot injections.