The high-mobility-group (HMG) protein gene HMGI-C is apparently involved in the genesis of a variety of benign human solid tumors with rearrangements of chromosomal region 12q14-15 affecting the HMGI-C gene. So far, no expression of HMGI-C has been found in adult tissues, and no data are available on the expression of HMGI-C in primary human malignant tumors of epithelial origin. Therefore, we analysed the HMGI-C expression patterns in 44 breast cancer samples and 13 samples of nonmalignant adjacent tissue by hemi-nested reverse transcriptase-polymerase chain reaction for HMGI-C expression. There was no detectable expression of HMGI-C in any nonmalignant adjacent breast tissues analyzed. In contrast, we found expression in 20 of 44 breast cancer samples investigated. In invasive ductal tumors, expression was noted predominantly in tumors with high histologic grade: 17 of 21 breast cancer samples with histologic grade 3 but only three of 16 samples with histologic grades 1 or 2 showed expression of HMGI-C. In addition, all seven lobular breast cancer samples tested did not express HMGI-C. From these results, we concluded that HMGI-C expression may be of pathogenetic or prognostic importance in breast cancer.