Generally, the karyotype profile of Down Syndrome has been reported to be full trisomy 21 in 92% of patients, mosaic trisomy 21 in 4% of patients and translocation involving chromosome 21 in 4% of patients in most of the population groups worldwide. But, karyotype analysis of 149 DS patients at the Human Genome Center, USM, during the past five years revealed that free trisomy accounted for 94.6%, mosaic trisomy 21 for 4.7% and translocation involving chromosome 21 in 0.7% of the Down Syndrome etiology in North East Malaysian population, indicating a low frequency of translocation DS in this region. Here, we report one case of translocation Down Syndrome encountered during karyotype analysis of 149 DS cases. Karyotype showed a robertsonian translocation where an entire extra chromosome 21 was attached to the centromere of one of the chromosome 14, resulting in a derivative chromosome 14 with attached chromosome 21. Karyotype analysis of the parents revealed a normal 46,XY pattern for father and 46,XX pattern for mother indicating that this robertsonian translocation had arisen de novo either prior to or at conception.