Background/Aims: The aim of the study is to evaluate the correlation between c-erb-B2 and CD44 overexpression and survival of patients with gastric cancer. Methodology: The paraffin blocks of 48 patients with gastric carcinoma were retrospectively analyzed. The pathological specimens were stained with CD44 and c-erb-B2 by immunohistochemical methods. Results: The positivity of c-erb-B2 was detected in 9 patients. In six of them, predominantly strong cytoplasmic staining was observed. The remaining three tumors were predominantly membranous stained. No correlation was found between the c-erb-B2 positivity and overall survival (OS). Seventeen specimens (35.4%) were CD44 positive, all localized in cell membrane. The median OS time of CD44 positive patients was worse than that of patients with CD44 negative (11 vs. 17 months, respectively). This difference was statistically significant 0=0.03). In 5 patients both CD44 and c-erb-B2 were detected as positive. However, there were 23 patients with both CD44 negative and c-erb-B2 negative. The median OS time for patients with both CD44 and c-erb-B2 negative was better than those of patients with both CD44 and c-erb-B2 positive (37 vs. 11 months, respectively, p=0.03). The relationship between CD44 and c-erb-B2 positivities and clinicopathological factors (p>0.05). Conclusions: Our results showed that there was no correlation between c-erb-B2 positivity and OS, except for CD44. In addition, we found significant association of simultaneous positivities of c-erb-B2 and CD44 with OS of patients with gastric cancer. CD44 alone can be taken as a prognostic factor and also simultaneous overexpression of CD44 and c-erb-B2 may be used as a marker of poor prognosis. © H.G.E. Update Medical Publishing S.A.