The authors report a case of twin pregnancy with complete hydatidiform mole coexisting with a live foetus (CHMCF) that developed gestational trophoblastic neoplasia (GTN). The patient with metastatic low risk GTN that developed resistance to single-agent chemotherapy achieved remission with combination chemotherapy. The patient’s condition, management of complication and literature review of etoposide, MTX, Act-D, Cyclophosphamide, and vincristine (EMA-CO) are presented in the hope that great caution can be exercised in managing CHMCF.