Phage display is a powerful tool in identifying specific antibody fragment binding to the target. Several strategies can be used to screen out a specific Fab from the phage library that binds to an antigen; it may be performed on immobilized targeted molecule, on the intact cells, or by other strategies. Antibodies with properties of recognizing tumor cell surface receptors in native conformation and ability to internalize to tumor cells through receptor binding are ideal carriers for targeted immuno-chemo and/or immuno-radiation therapy. This chapter describes a unique bio-panning method to screen out a Fab fragment against human epithelial growth factor receptor (EGFR) from a naive human Fab phage library for potential targeted therapeutic application on EGFR overexpressed cancers.