Estrogen receptors (ERs) have recently been reported to be present in carcinomas of stomach, an organ that has so far been considered as nontarget for sex hormones. Cathepsin D is an estrogen-regulated lysosomal protease that has been overexpressed in breast cancer. ER and cathepsin D immunohistochemical expression were studied in this research in order to estimate their association to known histopathological and clinical parameters and their possible prognostic significance as well. Sixty-two patients with gastric adenocarcinomas were included in this study. The cancers were studied immunohistochemically concerning ER positivity in tumor cell nuclei and cathepsin D cytoplasmic expression. Nuclear ER staining was detected in tumor cells of 25% of male and 27% of female patients. ER positivity was demonstrated mainly in the well and moderately differentiated carcinomas; 87.5% of ER(+) tumors were also characterized as cathepsin D positive and a significant correlation between ER and cathepsin D positive expression was demonstrated (P < 0.05). Cytoplasmic cathepsin D expression was observed in carcinomatous cells of 70.9% of gastric tumors. Early tumor stage and good differentiation were significantly associated with increased cathepsin D expression (P < 0.05, P < 0.001). Histologic type, degree of differentiation and tumor stage were significantly correlated to survival (P < 0.05, P < 0.001 and P < 0.001). The patients who were cathepsin D(+) had a significant prognostic advantage over the cathepsin D(-) patients (P < 0.001). The presence of ER and estrogen-regulated cathepsin D indicates the involvement of sex hormonal factors in these tumors and cathepsin D positive expression in tumor cells seems to be related to better prognosis. Their biological, clinical, and prognostic roles remain to be further elucidated.