Expression profiling studies using microarrays and other methods have shown that microRNAs (miRNAs) are dysregulated in a wide variety of human cancers. The up-regulation of miR-221 has been reported in carcinomas of the pancreas, breast, and papillary thyroid, as well as in glioblastoma and chronic lymphocytic leukaemia. In prostate cancer, however, down-regulation of miR-221 has been repeatedly confirmed in miRNA expression studies. Also unique to prostate cancer, and found in more than 50% of patients, is the aberrant expression of a known oncogene, the TMPRSS2:ERG fusion. To date, there has been no published study describing miRNA associations in prostate tumours that overexpress the ERG oncogene from the TMPRSS2:ERG fusion transcript. Herein we report that in a large and diverse cohort of prostate carcinoma samples, miR-221 is down-regulated in patients with tumours bearing TMPRSS2:ERG fusion transcripts, thus providing a link between miRNA and gene fusion expression.