Different origins for trisomy 15 mosaicism confined to the placenta have been suggested. We have analysed the data on trisomy 15 mosaicism in EUCROMIC. Trisomy 15 mosaicism or non-mosaic feto-placental discrepancy on CVS was registered in 0.027 per cent of samples karyotyped (34/126 465): 28/34 had confined placental mosaicism (CPM), 1/34 was probably true fetal mosaicism and 5/34 could not be classified. In 17 of the 28 pregnancies with CPM, cytogenetic information existed on both cytotrophoblast lineage (direct CVS preparation or short-term incubation) and extra-embryonic mesoderm, EEM (villus culture): CPM was of type I (restricted to the cytotrophoblast) in 5/17 (29 per cent); type II (restricted to the EEM) in 4/17 (24 per cent) and type III (both cytotrophoblast and EEM) in 8/17 (47 per cent). Testing for uniparental disomy (UPD) for chromosome 15 in the fetus or child was done in nine cases, showing upd(15)mat in 1/9, and biparental inheritance in 8/9. Upd(15)mat, clinically diagnosed due to Prader Willi syndrome, but without DNA analysis, was registered in one additional liveborn child. Analysis of these 17 cases, in conjunction with 10 similar reports in the literature also having cytogenetic data from both cell lineages, indicates two categories of trisomy 15 CPM. One has a high proportion of trisomic cells, often with a type III distribution, and an observed high risk of UPD and adverse pregnancy outcome. The second has lower proportions of trisomic cells, primarily of type I or II distribution, and a lower empirical risk of UPD or pregnancy loss. Based on this cytogenetic analysis, supported by the available DNA data, we suggest that, in contrast to trisomy 16 CPM, the trisomic cell line originates from a meiotic error in only about 50 per cent of cases of trisomy 15 CPM, the rest being the result of post-zygotic, mitotic non-disjunction. Despite this, we recommend amniocentesis following the finding of a mosaic or non-mosaic trisomy 15 by CVS, in order to exclude both UPD and potential true fetal mosaicism.