Here we report on a girl with minor facial anomalies, cleft palate, seizures, microcephaly, psychomotor retardation, and a congenital heart defect. Complex of cytogenetic methods [GTG-banding, spectral karyotyping (SKY), fluorescence in situ hybridization (FISH), multicolor banding (mBAND), and comparative genomic hybridization (array CGH)] showed complex chromosomal rearrangements (CCRs) involving chromosomes 6, 10, and 11 and 4 deletions at the breakpoints. Her father had an unrelated translocation between chromosomes 3 and 16, suggesting the possibility of an autosomal dominant trait that predisposes to complex synapses and recombination between multiple chromosomes during meiosis. This study demonstrates the power of combining available chromosome analysis technologies in resolving CCR.