Monoclonal antibodies (MAb) are firmly established diagnostic adjuvants both in vitro and in vivo. Their potential for immunotherapy is highly promising. Antigenic heterogeneity of cells within the same tumor is a well known phenomenon; however, no large-scale studies are available to ascertain to what degree metastases maintain the immunophenotype of the primary tumors. For that purpose, we studied 54 commonly epithelial malignancies using immunohistochemistry (IHC) with a panel of seven frequently used MAb recognizing a gamut of membrane and cytoplasmic antigens (AE-1, CAM 5.2, B72.3, MC10, anti-carcinoembryonic antigen (anti-CEA), epithelial membrane antigen (EMA), and human milk fat globule (HMFG)). The number of metastases per primary tumor ranged between 1 and 26, with a total of 344 tissues studied. Metastases were located in regional and distal lymph nodes as well as in a diversity of organs (pancreas, adrenal, colon, spleen, soft tissues, etc). Only those cases in which all the tissues were obtained from a single surgical procedure and, therefore, uniformly fixed and processed, were selected. All the metastases from three cases (5.5%) were found to express one or two antigens not present on their primary. In no case did all metastases from a positive primary become negative for one MAb. Twelve cases (18.5%) showed modifications of the phenotype in one or more metastases. This study demonstrates that a broad phenotypic variation does not follow when tumors metastasize, and that it is, therefore, safe to foretell the metastatic immunophenotype based upon that of the primary tumor.