An enzyme‐linked immunosorbent assay (ELISA) was developed to measure soluble erbB‐2 protein in culture supernatants of various human cell lines and sera of patients suffering from recurrent breast carcinoma. Soluble erbB‐2 protein was demonstrated in culture supernatants of cell lines that expressed high levels of erbB‐2 protein as shown by western blot analysis of cell lysates. Increased levels of the protein, 40‐ to 190‐fold higher than in healthy controls, were demonstrated in sera of 3 out of 12 patients with breast carcinomas. On immunohistological study of tumor tissues from 9 patients, high immune reaction with the anti‐ erbB‐2 protein antibody was observed in 2 cases. These were two of the three patients who had elevated levels of erbB‐2 protein in serum (a sample was not available from the third patient). These results raise the possibility that soluble erbB‐2 protein level in serum can be used as an indicator for spread of carcinomas that overexpress erbB‐2 protein.