Background/Aims: Epidermal growth factor (EGF) is involved in cancer development and proliferation. We measured preoperative serum EGF, and serologically investigated the clinical significance of EGF expression in gastric cancer. We also performed immunohistological staining at the same time, and investigated its relationship with serum EGF. Methodology: There were 79 patients who underwent surgery for gastric cancer. For the measurement, one-step sandwich EIA was performed. Of 79 cases of gastric cancer in which the serum EGF level was measured, EGF immunostaining was performed in 50 cases. Results: In Serology, the EGF level was 345.6 +/- 260.6pg/mL in m similar to sm cases, and 212.2 +/- 170.4pg/mL in mp-si cases (p<0.05). The EGF level was 294.4 +/- 236.0pg/mL in ly0 cases, and 194.2 +/- 142.5pg/mL in lyl-3 cases (p<0.05). The EGF level was 323.5 +/- 233.4pg/mL in cases staged IA similar to IB, and 202.8 +/- 176.8pg/mL in cases staged II similar to IV (p<0.05). In immunohistology the EGF positivity rate was 36.4% in the differentiated types, and 67.9% in the poorly differentiated types (p<0.05). The EGF positivity rate was 25.0% in m-sm cases, and 63.1% in mp similar to si cases (P<0.05). Conclusions: The above findings suggest that EGF uptake by cancer cells increases when cancer cells are poorly differentiated, and that invasion in the surrounding tissue is severe.