The development of accurate and sensitive methodologies to detect small chromosomal imbalances (<3 Mb) is extremely important in clinical diagnostics and research in human genetics. The technique of array-comparative genomic hybridization (CGH) using BAC and PAC clones is very sensitive methodology and is rapidly becoming the method of choice for high-resolution screening of genomic copy-number changes. An alternative methodology to CGH is the multiplex amplifiable probe hybridization (MAPH) methodology, a DNA based method that allows the accurate and reliable determination of changes in copy number in "known" or "unknown locations" in the human genome. MAPH uses probes of 100-500 bp in size, that can be specifically designed for any gene or locus in the genome and cover any gene exons, the subtelomeric or subcentromeric regions, any chromosomal segment, a whole chromosome or the total human genome. MAPH can provide extremely high resolution and enable the sensitive detection of loss or gain of genomic DNA sequences as small as 150 bp. Very recently we succeeded in the advancement of MAPH from gel and capillary analyses to microarrays. The array-MAPH methodology offers an alternative methodology to array-CGH and provides a new sensitive microarray-based method including several advantages for the detection of copy number changes in the human genome.