Aim: Upper gastrointestinal tract carcinomas are major health problem around the world. Esophageal cancer (EC) is usually diagnosed at an advanced stage; therefore most therapeutic approaches are palliative. The aim of the study was to investigate the possible relationship between serum activities of paraoxonase (PON1) and arylesterase (ARE), and clinicopathological characteristics in EC. Method: Forty patients with EC and twenty seven healthy subjects were included in the study. The diagnosis of esophageal cancer was established by endoscopic examination of the esophagus and by biopsy confirmation. PON and ARE activities were determined by or with spectrophotometrically using paraoxon and phenyl acetate as substrates, respectively. Mann-Whitney-U test was used for statistical analysis. Result: The mean serum PON and ARE activities were significantly higher in the cancer group compared to healthy controls. Besides, mean values of serum PON and ARE activities decreased in stage 3 and stage 4 EC patients compared with stage 2 EC patients. This decrease was statistically significant. There were no statistically correlation between other clinicopathological characteristics and serum PON and ARE activities in this EC patient group. Conclusion: This is the first report on serum PON and ARE activities in patients with EC. Our results indicate that low serum PON and ARE activities may be an important indicator for advanced stage in EC. But these preliminary results need to be verified by further prospective studies for the early diagnosis of the tumor, for the detection of clinical relapse and for the monitoring of follow up treatment.