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Since our publication, which first defined the malignant potential of placental site trophoblastic tumor (PSTT), we have had a keen interest in this rare, unique entity. This histologic entity is noted by its monomorphic population of trophoblast-like cells which are classified as originating in the intermediate trophoblast. These cells contain hymman placental lactogen (HPL). This is in contrast to cytotrophoblastic and syncytiotrophblastic tissues as the histologic, cytologic and immunohistochemical stain characteristics are disparate. Its rarity and the wide spectrum of clinical behavior combined with the lack of sensitivity of serum levels of beta hCG in predicting disease recurrence and spread have lead to anecdotal reports outlining clinical management. Most discerning to the clinician is the high mortality of metastatic placental site trophoblastic tumor. At our institution, we have treated two patients with a metastatic disease with a successful conclusion. The durability of responses is 3 and 8 years. This report will present these patients in detail and define the important characteristics of successful treatment. The use of dose-intensive, multi-agent chemotherapy, early intervention when metastatic disease is discovered, imaging techniques to define disease spread, surgery for localized disease and the use of growth factors, most notably granulocyte colony-stimulating factor (G-CSF), are the fundamentals of clinical care of placental site trophoblastic tumor in patients with metastatic placental site trophoblastic tumor.