Abstract Objective To present prenatal diagnosis of mosaic trisomy 8 and to review the literature. Materials, Methods, and Results A 34-year-old woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+86/46,XY31. Repeated amniocentesis at 21 weeks of gestation revealed a karyotype of 47,XY,+84/46,XY77. Interphase fluorescence in situ hybridization analysis of uncultured amniocytes showed 25% (5/20) mosaicism for trisomy 8. Array comparative genomic hybridization (aCGH) and quantitative fluorescent polymerase chain reaction (QF-PCR) analyses of uncultured amniocytes revealed no genomic imbalance in chromosome 8. The result of QF-PCR excluded uniparental disomy 8. At 23 weeks of gestation, the woman underwent amniocentesis and cordocentesis at other hospitals. Amniocentesis revealed a karyotype of 47,XY,+86/46,XY10. Cordocentesis revealed a karyotype of 47,XY,+81/46,XY29. Level II ultrasound findings were unremarkable. The parents decided to continue the pregnancy. A 1373-g male baby was prematurely delivered at 29 weeks of gestation. The peripheral blood had a karyotype of 47,XY,+81/46,XY29. The infant had normal growth and mental development at 4 months of age. Conclusion Fetuses with mosaic trisomy 8 are compatible with viability and can have a favorable outcome. QF-PCR and array comparative genomic hybridization have the limitation of detection of low-level mosaicism. We suggest that in instances of repeated amniocentesis for confirmation of mosaic trisomy 8, follow-up investigations should include interphase fluorescence in situ hybridization studies on uncultured amniocytes, uniparental disomy tests, and detailed ultrasound examinations.