MicroRNAs (miRNAs) are small non-coding RNAs that inhibit expression of specific target genes at the posttranscriptional level. MiRNAs are often found to be misregulated in human cancer, and they can act as either potent oncogenes or tumour suppressor genes. Here we show that a germline mutation in mature miR-125a is highly associated with breast cancer tumorigenesis, suggesting that miR-125a is likely to function as a tumour suppressor gene in human cancer.