BACKGROUND: Obesity is associated with an aggressive form of prostate cancer and with alterations in androgen and estrogen metabolism. We hypothesized that changes in components of the sex steroid receptor axis may contribute to the clinical aggressiveness of prostate cancer in obese patients. METHODS: A database was assembled containing clinical and pathological variables from 539 patients treated with radical prostatectomy at a single urban hospital between 1994 and 2002. Tissue microarrays were constructed from representative patients and expression of androgen receptor (AR), PSA, estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), and aromatase was examined. RESULTS: Higher BMI correlated strongly with black race, the presence of extra-capsular extension, and higher pathologic stage. Expression of AR, PSA, ERbeta and aromatase in cancerous epithelial cells did not differ according to obesity status. However, decreased expression of ERalpha and aromatase was observed in the stromal compartment surrounding non-cancerous acini in obese patients. CONCLUSION: We confirm the previously reported associations between obesity and aggressive clinical and pathologic features in our single-institution, urban teaching hospital. In comparing obese versus non-obese patients, there was no difference in expression of androgen or estrogen related proteins in cancerous epithelial cells. However, there was a down-regulation of ERalpha and aromatase in the stroma of obese patients. Our data suggest obesity may cause stromal changes in the sex steroid production and signaling pathways which may affect prostate cancer growth via intracrine/paracrine mechanisms.