Cervico-isthmic pregnancy is a rare form of ectopic pregnancy and is defined as the implantation of a fertilized ovum in the cervico-isthmic portion. The cause is unknown; local pathology related to previous cervical or uterine surgery may play a role, given an apparent association with a prior history of curettage or cesarean delivery. Transvaginal ultrasonography and beta-human chorionic gonadotrophin assays are useful for diagnosis. Here we report a case of spontaneous twin cervico-isthmic pregnancy in a grand multiparous patient who was diagnosed early in the first trimester with transvaginal ultrasonography. The pregnancy was terminated successfully with methotrexate. Methotrexate seems to be most successful at early gestational ages.