Abstract The HIC1 gene is a transcriptional regulator commonly methylated in a variety of human cancer. Thirty-three invasive ductal carcinomas of the breast and 21 matched normal breast tissues were analysed for HIC1 promoter methylation, and allelic loss of a 700 kb region spanning the gene locus. At least one genetic or epigenetic abnormality was found in 27 of the carcinomas tested (82%). Promoter methylation was demonstrated in 21 carcinomas (64%), and nine normal tissues (43%), whereas 18 malignant tumors (54%) showed allelic loss. Concomitant loss of heterozigosity and promoter hypermethylation in the region spanning HIC1 was detected in eight carcinomas (24%) suggesting that in this subset of tumors both copies of the gene are functionally lost. These observations support a role for the HIC1 gene in the pathogenesis of breast ductal carcinomas.