Disclosed are methods for identifying genetic mosaicisms in cell populations. Suitable cell populations include, e.g., biopsy or body fluid samples or cultures of cancer cells. The method includes performing array-based comparative genomic hybridization (CGH), wherein a plurality of cloned genomic nucleic acid segments is provided in a plurality of identical replicas, each cloned segment immobilized to a discrete and known spot on a substrate surface to form the array, and the cloned genomic nucleic acid segments comprise a substantially complete first genome of a known first karyotype. The invention also provides methods for optimizing performance of an array-based comparative genomic hybridization (CGH).