This chapter provides basic information for quantifying soluble epidermal growth factor receptor (sEGFR) isoforms in human sera using an acridinium-linked immunosorbent assay (ALISA) developed by Baron and coworkers (1 ). This ALISA has been shown to be specific for epidermal growth factor receptor (EGFR) and the isoforms of EGFR encoded by alternate transcripts (i.e., sEGFRs); it, therefore, does not detect other EGFR/ErbB receptor family members, i.e., ErbB2, ErbB3, or ErbB4. In addition, this ALISA recognizes EGFR and sEGFR isoforms that contain subdomains I–IV of the extracellular domain, but it does not recognize EGFR isoforms lacking subdomain IV. The ALISA described here also may be useful for determining EGFR and sEGFR concentrations in lysates of cultured cells, conditioned culture medium, or tissue/tumor specimens, as well as in other human body fluids such as serum, plasma, ascites, urine, saliva, and cystic fluids.