A 39 year-old patient with long-standing diagnosis of pelvic endometriosis had been treated for over twenty years with oral contraceptives (OCs). A year prior to admission to the gynecological ward, an ultrasonographic examination revealed three hepatic lesions, which were not reported in previous liver sonography. These lesions progressed during OC use, over the next six months. Liver function tests were normal. Liver scan, CT and ultrasound imaging techniques supported the diagnosis of solid hepatic tumors. These lesions developed concomitantly to long-term use of OCs, therefore discontinuation of therapy was mandatory. Six months later, the patient was hospitalized due to pelvic pain. She underwent total abdominal hysterectomy and left salpingo-oophorectomy (the right adnexa had been removed years before). Due to the patient's young age, hormone replacement therapy was indicated. The preferred preparation was transdermal estradiol due to the fact that systemic absorption has no hepatic first-pass effect and therefore exerts minimal influence on liver enzymes and functions. Serial ultrasonographic examinations, performed while under treatment with transdermal estradiol, showed complete regression of the hepatic lesions over a period of two years. Our report demonstrates regression of multifocal hepatic tumors despite transdermal estradiol replacement therapy.