Chromosomal microarray is considered a first-line genetic test in several distinct clinical situations, each with its own supporting evidence:

• A child or adult with unexplained developmental delay or intellectual disability. Professional guidance recommends chromosomal microarray as a first genetic test to consider, ahead of a standard karyotype, because it identifies a relevant genetic finding in roughly 1 in 5 to 1 in 7 individuals tested, compared with only about 1 in 30 to 1 in 50 with a karyotype alone. Current guidance also recommends that exome or genome sequencing, a newer test that reads the genetic code letter by letter, be considered alongside or after chromosomal microarray in this group, since the two tests find different kinds of genetic change and together identify meaningfully more causes than either alone.

• A child with an autism spectrum diagnosis, particularly when accompanied by any additional physical or developmental feature, since a meaningful share of children with autism also carry an identifiable copy number variant.
• A child born with multiple unexplained physical differences or birth differences affecting more than one body system, where a single unifying genetic explanation is being sought, again often alongside sequencing-based testing.
• A pregnancy with a structural anomaly found on ultrasound. When invasive testing such as chorionic villus sampling or amniocentesis is already being performed for this reason, professional bodies recommend chromosomal microarray in place of, or in addition to, a standard karyotype, since it identifies an additional clinically meaningful finding in roughly 6 in 100 such pregnancies that a karyotype alone would have called normal.
• A stillbirth or pregnancy loss where a cause is being investigated. Chromosomal microarray can be performed directly on fetal tissue and does not require living, dividing cells the way a karyotype does, so it succeeds far more often on stillbirth samples and identifies a genetic abnormality in substantially more cases than karyotyping alone.
• A pregnancy without a structural anomaly, for example where testing is being done because of parental anxiety or a positive screening result. Here the additional information gained above a standard karyotype is smaller, on the order of 1 to 2 in 100 pregnancies, and this lower yield is part of the conversation a genetic counselor has with parents before testing.

Chromosomal microarray is not typically the first test recommended for an early, first-trimester pregnancy loss, where a standard karyotype usually remains the starting point, and it is not a substitute for a full clinical evaluation; it is one part of a broader work-up that a geneticist or genetic counselor tailors to the specific situation.