Abstract: Human monoclonal anti-tumor antibodies are isolated from fusion phage single-chain Fv and V.sub.H antibody libraries constructed from the peripheral blood lymphocytes of immunized cancer patients. Antibodies that bind to tumor cells of the same kind as the patient's are selected, and antibodies that also bind to a human normal cell type are removed. The remaining fusion phage antibodies are cloned and then are tested for binding to at least two normal human cell types. Antibodies that fail to bind to the normal cells are further tested for binding to a panel of tumor cells, typically including the original tumor type and several related and unrelated tumors. Human monoclonal antibodies that bind specifically to the original tumor or also to some other tumors, or that bind to the original tumor and cells from the same developmental lineage, are obtained and sequenced. The selected antibodies can be used to design molecules which are potentially useful for various diagnostic and therapeutic purposes.