The prenatal diagnosis of an 11q;22q translocation in a triplet pregnancy detected at the time of chorionic villus sampling (CVS) because of advanced maternal age is reported. Karyotypes obtained from two apparently different CV samples showed the balanced form of translocation, while the one obtained from a third empty sac showed the unbalanced form: 46,XX,-22,+der(22)t(11;22). Second-trimester amniocentesis confirmed the balanced translocation in one of the two viable fetuses and a normal karyotype in the other. The detected karyotypes derived from two different types of meiotic segregation, alternate and adjacent 1. To our knowledge, this is the first reported case of an unbalanced karyotype not due to a 3:1 meiotic segregation of this specific translocation.