Abstract: The invention provides monoclonal antibodies that bind the estrogen receptor ? (ER ?) when phosphorylated at serine 118 (Ser118) in the N-terminal domain, but do not bind to ER ? when not phosphorylated at this site. Also provided are methods for determining the phosphorylation of ER ? in a biological sample, profiling ER ? activation in a test tissue, and identifying a compound that modulates phosphorylation of ER ? in a test tissue, by using the disclosed monoclonal antibodies. The sample or test tissue may be taken from a subject suspected of having cancer, such as breast cancer. Kits comprising the phospho-ER ? (Ser118) monoclonal antibodies of the invention are also provided.