The routine examination of prenatal chromosomal diseases are chromosome banding analysis of short-term cultured chorionic villus cells, amniotic fluid cells, umbilical cord blood cells, and lymphocytes in peripheral blood, or the analysis of X small body and Y small body in uncultured interphase cells. The above methods played an important role in diagnosing chromosome diseases, but single banding methods have many shortcomings such as long test cycle, cultured failure with high frequency because the material is easily polluted when being drawn. Moreover, it can't detect tiny distortion of chromosome. The fluorescence in situ hybridization (FISH), advanced in recent years, is a chromosome and genetic analysis technology with high sensitivity and specificity, which is a supplement to classic genetics method, playing an important role in chromosome disease diagnosis. This method not only can detect chromosome abnormal quantity, but also can reliably verify tiny distortion and the source of abnormal segment which can not be detected by single chromosome banding analysis. Now, fluorescence in situ hybridization has been widely used to diagnose chromosome abnormality including aneuploidy screening in peripheral blood lymphocytes, amniotic fluid, fluffy cells, fetal nucleated from its mother, peripheral blood, and trophocytes from collection of cervical washing, and so on, which is not suitable for conventional chromosome anomaly analysis and preimplantation genetic diagnosis (GPD). Conventional cytogenetic methods and molecular cytogenetics methods to diagnose chromosome disease will be reviewed in this paper.