Investigations of individuals with multiple CM has shown that about 40% of these have apparently balanced chromosomal rearrangements and suggests that micro imbalances may be a common finding. The introduction of aCGH has doubled the detection rate of genomic micro imbalances in individuals with multiple CM or dysmorphism. Copy number varia­tion in the human genome is now better understood and its implications in diagnosis and in genetic coun­seling are being rapidly uncovered. Submicrosco­pic chromosomal imbalances have been detected by aCGH in 10 to 30% of patients with otherwise unex­plained CM. This method can also be used to make cytogenetic diagnosis more accurate and precise, since the size of a deletion and even the break points can be determined. This is important for the under­standing of phenotype/genotype correlations and for the identification of disease-related genes. The appli­cation of aCGH in cases that are considered to have “balanced”translocations, could detect whether, in the vicinity of the breakpoints, the chromosomal mate­rial is deleted or duplicated (i.e., is in an unbalanced form), or is truly balanced. In addition, the applica­tion of aCGH technology has the potential to improve our understanding of the normal quantitative variants of the human genome. Array CGH will have a major impact on pre- and postnatal diagnoses, genetic coun­seling and healthcare.