Cytogenetically visible aberrations of chromosomal region 12q14-15 in a variety of frequent benign human tumors reflect rearrangements of the HMGI-C gene. The mechanisms by which the HMGI-C gene contributes to tumorigenesis are mostly unknown, although frequently aberrant transcripts containing exons 1 to 3 of HMGI-C and ectopic sequences from other genes due to breaks within the third intron of HMGI-C are detectable. This is the first report analyzing human tissue samples mainly of mesenchymal origin by a highly sensitive polymerase-chain-reaction-based approach detecting HMGI-C expression. We found HMGI-C expression in embryonic tissue but no expression in any of several adult tissues tested except for two myometrial tissues. These data suggest that HMGI-C is mainly expressed in human tissues during embryonal and fetal development. Thus, its particular role for tumor development may be due to the expression of at least exons 1 to 3 rather than to the formation of fusion transcripts.