We may currently be living in a time of endless possibilities for cytogenomic research and diagnostics. Since one of the main goals in human genetics, in particular, seems to be to find a single comprehensive approach that replaces all others, including (molecular) cytogenetics, previous standard techniques have been and continue to be discredited. Although the limitations of array comparative genomic hybridization/ chromosome microarray are well known, there is a tendency not to verify the nature of the underlying chromosomal rearrangement when one or more copy number variations (CNVs) are found using this molecular genetic approach. Here we list examples of what the presence of a CNV can mean at the karyotypic level. We would like to emphasize that only a (molecular) cytogenetic examination of the index patient and the parents can provide a comprehensive understanding of the underlying genetic change and thus form the basis for sound genetic counseling.