AIM: To detect the expression of CXC chemokine receptor 4 (CXCR4) and CC chemokine receptor 7 (CCR7) in normal esophageal mucosa, Barrett' s esophagus (BE), esophageal adenocarcinoma (EADC), and esophageal squamous cell carcinoma (ESCC), and to investigate their clinical significance. METHODS: The expression of CXCR4 and CCR7 in 56 normal esophageal mucosal specimens, 80 BE specimens (including 22 cases of BE with multifocal atypical hyperplasia), 25 EADC specimens, and 48 ESCC specimens was examined by immunohistochemistry. The expression levels of CXCR4 and CCR7 were then quantified and analyzed statistically. RESULTS: The positive expression rates of CXCR4 and CCR7 in BE, EADC and ESCC were significantly higher than those in normal esophageal mucosa (CXCR4: 78.75%, 68.00%, 83.33% vs 39.29%; CCR7: 60.00%, 60.00%, 58.33% vs 30.36%; all P < 0.01). However, there were no significant differences in the positive expression rates of CXCR4 and CCR7 among BE, EADC and ESCC. The positive expression rates of CXCR4 were significantly higher than those of CCR7 in both BE and ESCC (P < 0.05 and 0.01). CXCR4 and CCR7 expression was not associated with gender, age, and lesion site in BE, EADC and ESCC, but correlated with tumor differentiation and lymph node metastasis in EADC (both P < 0.05) and TNM stage, lymph node metastasis, and differentiation in ESCC (all P < 0.05). A significant correlation was noted between CXCR4 and CCR7 expression in BE and EADC (r = 0.262, 0.490), but not in ESCC (r = 0.076). CONCLUSION: Combined detection of CXCR4 and CCR7 expression may contribute to more accurate diagnosis of BE, EADC and ESCC. High expression levels of CXCR4 and CCR7 can be used as important parameters for evaluating tumor invasion and metastasis in both EADC and ESCC.