Novel monoclonal antibodies and binding fragments thereof specific to human breast cancer, lung cancer, colon cancer and other cancers. The monoclonal antibody does not bind to the cell surface of normal human tissues. The corresponding cancer-specific antigen with an apparent molecular weight of 150 kd and polynucleotides encoding the antigen and the CDR regions of the antibody are Also disclosed are methods for diagnosis, prognosis and treatment of human breast cancer. The antibodies have tumor specificity and are useful for therapy, diagnosis, monitoring, detecting and imaging of cancers. The antibody-recognized cancer-specific surface antigens can serve as targets for detecting, diagnosing, inhibiting or killing cancer cells.