Epidermal growth factor receptor (EGFR) plays a critical role in proliferation, apoptosis, angiogenesis, invasiveness and distant metastasis of tumors. In this study, the tumor targeting properties of anti-EGFR monoclonal antibody (mAb) LA22 in a colon cancer mouse model are evaluated. The results from flow cytometry assay and immunofluorescent staining clearly showed that HT-29 human colon cancer cells were EGFR positive, and the binding of mAb LA22 to the HT-29 cell surface was specific. The saturation binding experiment of ¹²⁵I-LA22 to HT-29 cells revealed that LA22 possessed moderate affinity to EGFR with the Kd value calculated to be 3.28±0.76 nM. The in vivo γ imaging demonstrated the specific accumulation of ¹²⁵I-LA22 in HT-29 tumor xenografts. The specific tumor targeting properties of mAb LA22 make it a good candidate for tumor targeted radioimmunotherapy of EGFR-positive tumors when it is labeled with therapeutic nuclides, such as ¹³¹I, ¹⁷⁷Lu, or ⁹⁰Y.