Submicroscopic gains or losses of chromosomal material are known as copy number variations (CNVs). Such CNVs are either connected with a disease or can also be (much more frequently) just a manifestation of human’s genetic range of variation. Besides cytogenetic visible copy number variations (CG-CNVs) first discovered as chromosomal heteromorphisms, and later e. g. as euchromatic variants (EVs), there are also submicroscopic CNVs (MG-CNVs). Especially the latter may be a headache for diagnostics as the same MG-CNV may be found in clinically healthy and diseased persons. A so-called two-hit model has been introduced to solve this puzzle. As this considers the number of CNVs present overall in a genome the question arises if CG-CNVs are considered enough in routine cytogenetic as well as MG-CNVs in array-comparative genomic hybridization analysis.