The normal diploid number of human chromosomes is 46, and was established by Tjio and Levan in 1956. This was a landmark in the history of human cytogenetics because, until then, human diploid constitution was believed to be 48. The impact of this discovery was soon felt in medical cytogenetics, when Lejeune et al (1959) reported that the common mental retardation disorder, Down syndrome [DS] was caused by trisomy of one of the G-group chromosomes, resulting in chromosome number 47 [Fig.9–1]. More examples of chromosomal aneuploidy leading to syndromes were reported the same year: Turner syndrome and Klinefelter syndrome (Ford et al., 1959; Jacobs and Strong, 1959) were caused by the loss (45,XO) and gain (47,XXY) of the X-chromosome, respectively. These examples highlight the importance of establishing the correct diploid number in man.