Cell-free fetal DNA in maternal circulation is detectable in early pregnancy, increases with gestational age, and decreases rapidly after delivery (1)(2)(3). It has been used for noninvasive prenatal diagnoses, such as fetal rhesus status and sex determination (4)(5), but whether cell-free fetal DNA originates from villous tissue or fetal cells circulating in maternal blood has not been determined. Complete hydatidiform mole lacks a fetal component, and DNA originating from a hydatidiform mole (molar DNA) that is detected in the maternal circulation is thought to originate from villous tissue. By analyzing by real-time PCR the amount of sex-determining region Y ( SRY ) DNA in maternal serum before and after delivery of a 46,XY complete hydatidiform mole coexisting with a normal 46,XX fetus, we have confirmed that the DNA in maternal blood originates from villous tissue. The patient was a 30-year-old gravida I, para 0. She was examined at our hospital at 20 weeks of gestation. Ultrasound examination showed a normally grown fetus without anomalies with a normal placenta, and a molar placenta. At 28 weeks of gestation, she spontaneously delivered vaginally a 1094-g female infant with a grossly normal placenta, and a molar placenta. …