The high-mobility-group (HMG) protein gene, HMGIC, is localized to chromosome 12, band q15, a region often rearranged in benign mesenchymal tumors, including uterine leiomyomata. Although some evidence suggests a role in regulation of cell proliferation, the precise function of HMGIC in the development or progression of these tumors remains unclear. We investigated HMGIC expression in 17 fetal tissues (adrenal, aorta, bone, brain, heart, intestine, kidney, liver, lung, muscle, ovary, placenta, skin, spleen, stomach, testis, and uterus) and 10 adult tissues (aorta, brain, cerebellum, fat, kidney, liver, lung, lymph node, myometrium, and spinal cord) by Northern blot and reverse transcriptase-polymerase chain reaction (RT-PCR) assays. Comparisons between HMGIC gene expression in tumor samples from 11 uterine leiomyomata and 7 normal matched myometrium or in vitro cell cultures (chorionic villi, placenta, myometrium, leiomyoma, and skin) were also performed. The gene was expressed in all fetal tissues tested but only in adult lung and kidney. HMGIC was also expressed in leiomyoma tumor samples containing t(12;14) and in all in vitro cell cultures. The pattern of HMGIC expression suggests that this gene is important in rapidly proliferating human fetal tissues. Restoration of expression in leiomyomata required dysregulation of HMGIC. Transcripts of HMGIC can also be detected after in vitro cell culture, suggesting that HMGIC expression may be affected by factors present in culture media and serum. Genes Chromosomes Cancer 25:316-322, 1999.