Abstract: Objective: To investigate the advantages and disadvantages of various molecular genetic techniques in prenatal screening and diagnosis of two fetuses with small supernumerary marker chromosome (sSMC). Methods: Amniocentesis were performed on the two pregnant women with high-risk fetuses detected by noninvasive prenatal tests (NIPT), and amniotic fluid samples were collected. The multiplex ligation-dependent probe amplification (MLPA) technique was used to detect the chromosomal aneuploidy of two fetuses, and the culture of amniotic fluid cells for analyzing G-band karyotype was performed at the same time. The chromosome microarray (CMA) was used to verify the fetus with high risk of trisomy 18, and MLPA was used to detect the microdeletion of Y chromosome of the fetus with high risk of sex chromosomal abnormality. The karyotypes of two fetal parents were analyzed by the G-banding technology. Results: The rapid diagnosis results of MLPA showed that the triploid of the partial 18p was found in Fetus 1, and that two X chromosomes and one Y chromosome with deletion of Yp were found in Fetus 2. The karyotype results of amniotic fluid samples showed 47, XY + Mar in Fetus 1 and 47, XX + Mar in Fetus 2. The CMA result of Fetus 1 was arr\[hg19\]18p11.32p11.21(136,227-15,099)×4. The microdeletion result of Y chromosome showed that there were deletions of SRY gene and AZFc region in Fetus 2. The karyotypes of two fetal parents were normal. Conclusion: NIPT is suitable for the prenatal screening of fetuses with sSMC. Different molecular genetic techniques have their own advantages and disadvantages in the prenatal diagnosis of sSMC. These results can be combined with each other to provide more detailed information for the clinical genetic consultation of fetuses with sSMC.