Multiple sites of phosphorylation on human estrogen receptor a (ERa) have been identified by a variety of methodologies. Now with the emerging availability of phospho-site-specific antibodies to ERa, the relevance of phosphorylation of ERa in human breast cancer in vivo is being explored. Multiple phosphorylated sites in ERa can be detected in multiple breast tumor biopsy samples, providing evidence of their relevance to human breast cancer in vivo. Published data suggest that the detection in primary breast tumors of phosphorylation at some sites in ERa is associated with a better clinical outcome while phosphorylation at other sites is associated with a poorer clinical outcome most often in patients who have been treated with tamoxifen. This suggests the hypothesis that phospho-profiling of ERa in human breast tumors to establish an ‘ERa phosphorylation code’, may be a more accurate marker of prognosis and/or response to endocrine therapy in human breast cancer.