A 5-month-old girl had a typical 12p trisomy syndrome due to a monocentric i(12p) present in a 46-chromosome complement that also included the translocation of all 12q onto the 8p telomere; i.e., her complex karyotype could be written as 46,XX,-8,-12, +der(8),t(8;12)(p23.3;cen),+i(12p). The present concurrence of a whole-arm q translocation and an i(p) for a single chromosome, along with six previous similar instances involving chromosomes 4, 5 and 9, suggests the following origin for such a special rearrangement: a centric fission in G1 initially yielding two telocentrics; at the next replication, the tel(q) translocates onto a nonhomologous telomere (centromere-telomere fusion), whereas the tel(p) becomes an i(p). This mechanism can be either meiotic or postzygotic and surmises that the translocated long arm retains a partial centromere, which subsequently is inactivated and loses its staining properties.