For patients with persistent or invasive gestational trophoblastic disease (GTD), systemic injection of chemotherapy is the treat­ment of choice if fertility is to be preserved. To prevent serious adverse effects after systemic use and possibly achieve better effects, direct local injection of chemotherapy into the tumor site, especially when in the myometrium, seems a reasonable alternative. A patient with a persistent molar pregnancy with myometrial invasion is presented. A plateau of β-hCG (human chorionic gona­dotropin) level around 550 mlU/mL was noticed for three weeks though systemic methotrexate (MTX) injection and repeat suction curettage had been performed. During the same period, a well-defined invasive complex with multiple vesicles in the myometrium was documented using transvaginal ultrasound (TYUS). Sonar-guided injection to the tumor using 50 mg MTX was performed uneventfully. An obvious shrinkage of the mass and declining β-hCG level were demonstrated after the procedure. The patient resto­red her menses after the operation and a fertility evaluation including serial β-hCG levels and hysterosalpingography showed them to be within the reference ranges. The successful outcome of this case encouraged us to treat localized invasive GTD using direct injection of MTX with the guidance of TYUS. Since no identical cases were found in our review of the English literature, more cases and similar regimens are needed to establish the safety and efficacy of this procedure.