Human antibodies were generated by Epstein-Barr Virus (EBV) immortalization of B cells derived from tumor draining lymph nodes of cancer patients. Antibodies were screened for reactivity in ELISA against a synthetic peptide corresponding to the protein core of the Polymorphic Epithelial Mucin (PEM). Epitopes within this region are in fact considered to be tumor specific since they are selectively exposed on tumor cells due to aberrant glycosylation. Human antibodies thus selected react in ELISA and immunohistochemistry with PEM-expressing tumor cells. This is the first demonstration of the existence of B cell immune response against selected epitopes of PEM and, in association with the cytotoxic T cell (CTL) response already demonstrated, represents the basis for the use of synthetic peptides as vaccines in cancer patients.