A 28-year-old Japanese woman had an invasive hydatidiform mole which was diagnosed by means of transvaginal ultrasonography. After the two initial courses of systemic methotrexate (MTX) therapy given over a period of weeks, the tumor was 14 mm in diameter and the surrounding blood supply remained rich. In addition to the two initial courses of systemic MTX therapy, local ultrasound-guided injection of MTX therapy was given three times, once per week. After the local MTX treatment, the betahCG level, which had been as high as 240 ng/mL, dropped to less than 0.1 ng/mL. We then gave two additional courses of systemic MTX therapy (once per week). More than 3 years have passed since the final systemic MTX therapy, and the patient's serum betahCG levels continue to be less than 0.1 ng/mL. An invasive mole can be treated with an ultrasound-guided local injection of MTX in addition to the established systemic MTX treatment.