The detection of gene mutation of epithelial growth factor receptor (EGFR) is important to predict the therapeutic effect of gefitinib. Recently, it was reported that examination of the activation of the downstream protein of EGFR is useful in the same way as the EGFR mutation. Therefore the purpose of the present paper was to determine whether activation of Akt and Erk, which are downstream proteins, and the EGFR gene mutation pattern was correlated. A total of 130 pulmonary adenocarcinomas were studied for the gene mutations of EGFR in exon 19 and 21, and the phosphorylation of Akt and Erk was investigated by immunostaining. The EGFR mutation was detected in 32%, the positivity of p-Akt was 51%, and the rate of p-Erk was 27%. The EGFR mutation-positive cases were the minority in p-Akt-negative cases, and the p-Akt expression was significantly associated with the mutation of EGFR (P=0.0014). In addition, there was a significant correlation between the L858R mutation and the expression of p-Akt (P=0.040). It is suggested that the activation of Akt is dependent on EGFR mutation pattern.