Monoclonal antibodies (MAbs) that are reactive with tumor associated antigens (TAAs) have led to many of the recent advances made in tumor immunology. At the present time, many of these MAbs have already been used in various aspects of patient management and in better understanding the biology of carcinoma cell populations. Because of their diversity, specificity and biological activity, these MAbs are potentially ideal agents for a variety of applications in malignant disorders such as, clinical diagnosis using serum assays, immunocytopathological analyses of effusions or fine-needle aspiration specimens, immunoscintigraphy, radioimmunoguided surgery and, with additional development, site directed immunotherapy. Nevertheless, their clinical application shows advantages and limitations. Optimization of their clinical use is actually under evaluation in several Institutions, including our Department. Many innovations have been developed over the last decade which may enhance their clinical efficacy. In this view, an optimal tumor targeting for diagnostic or therapeutic applications may require a better choice of radiotracer, generation of new molecules and the characterization of TAAs at the target level.