It was shown the functional crosstalk between ERRalpha and ERalpha in breast cancer, however, the biological significance of estrogen-related receptor alpha (ERRalpha) remains largely unclear. Therefore, we examined the expression of ERRalpha in 39 primary human breast cancer tissues and 19 matched normal tissues using RT-PCR and immunohistochemistry in the context of the aromatase, ERalpha and proliferation markers (c-myc, Ki-67) expression. Compared to the normal breast tissue, breast cancer tissues showed a slightly higher expression level of ERRalpha mRNA (mean 46.2+/-S.D.42.0, 57.7+/-S.D.58.7, respectively). However, ERRalpha mRNA levels in breast cancer tissues showed greater diversity than in normal tissues. Immunohistochemical analysis of breast cancers revealed perinuclear and cytoplasmic localization of ERRalpha. Our study shows that there is no correlation between ERRalpha and ERalpha expression. We demonstrated a positive correlation between ERRalpha and c-myc at the transcriptional level and statistically significant positive correlation between aromatase and the ERRalpha at protein level. It seems that ERRalpha could play an important role in the alternative pathway to classical estrogen receptors-dependent pathway in cell signaling. Development and use of ERRs modulators might lead in the future to design new well-tolerated and individualized therapeutic agents.