We report 2 cases of plasma cell dyscrasia presenting with significantly elevated serum CA125 levels. The serum levels of CA125 from these patients correlated well with their serum M-protein levels. One patient had an IgG-ĸ type extramedullary plasmacytoma with the culture supernatant from lymph node plasma cells showing a considerably high level of CA125 activity. The serum IgG fraction purified using a protein A column was devoid of any detectable CA125 activity, negating that the serum IgG M-protein from this patient might respond with a false-positive result in the CA125 immunoradiometric assay. The other patient had an IgG-λ type plasma cell leukemia with the culture supernatant from peripheral mononuclear cells also showing a high level of CA125 activity. These observations may suggest that in plasma cell dyscrasias the CA125 antigen is spontaneously produced by tumor cells.