Mucin 16 (MUC16) is a 3-5 millon Da membrane spanning mucin with a 284 aa C-terminal domain, a 12,068 aa N- terminal domain, and a tandem repeat domain sandwiched in between. CA- 125 is the 156 aa repeating peptide epitope of MUC16. The tandem repeat domain is composed of up to 60 repeats. The antibodies OC125 and M11 recognize the tandem repeat sequence. CA-125 is expressed in two forms, as a membrane bound protein at surface of cells that undergo metaplasia into a Mullerian–type epithelium or in soluble form in bodily fluids. Normal bronchial, endometrial, ovarian and corneal epithelial cells express MUC16 released from the surface by proteolytic cleavage. Glycosylation around cleavage site regulates cleavage of the ectodomain. CA125 is used widely for the diagnosis and monitoring of ovarian cancer patients and progression of epithelial ovarian cancers. CA125 levels of greater than 35 U/mL are considered an indication of potential malignancies. Recent studies suggest that a ROMA (Risk of Ovarian malignancy Algorithm) using levels of CA125 and HE4 in serum is likely to give a test that is very sensitive and specific in identifying ovarian cancer patients. CA-125 is being investigated as a target for immunotherapy in the treatment of epithelial ovarian cancers. Oregovomab behaves as an active immunotherapeutic agent and forms immune complexes with serum soluble CA-125 and triggers CA125-specific immune responses. Anti-CA-125 antibodies conjugated to cytotoxic drugs are also currently being studied in animal models. Elevated CA-125 levels are also seen in other cancers including endometrial, breast, lung, liver, stomach bladder and nonHodgkin lymphoma. Elevated CA125 levels have also been found in benign conditions like endometriosis, pregnancy, liver disease, congestive heart failure and infectious disease like tuberculosis.