An immunohistochemical and flow cytometric DNA study of two cases of metastasizing placental site trophoblastic tumor are presented. One patient aged 29 died rapidly of widespread metastases despite hysterectomy and multiagent chemotherapy. The patient had a low level of serum HCG. The course was complicated by the presence of a nephrotic syndrome. The other patient aged 34 had a vaginal metastasis and high levels of serum HCG, and was alive without disease for 9 years after hysterectomy and chemotherapy. Histologically, these tumors were characterized by a monomorphic trophoblastic cell population, probably derived from intermediate trophoblast in the placental site. The mitotic rate in these tumors was 2-4/10 high-power fields. Immunohistochemically, many tumor cells contained human placental lactogen and placental alkaline phosphatase. Beta-unit chorionic gonadotropin was present in many cells of the second patient, and only focally in the first. All specimens including the curettaged and metastatic lesions revealed a diploid DNA content in both cases. Neither DNA ploidy nor S-phase fraction was associated with survival of patient. Since predicting the biologic behavior of placental site trophoblastic tumor is very difficult, making a correct diagnosis on endometrial curettings, hysterectomy, and monitoring serum HCG level is essential in patients with this tumor.