OBJECTIVE The article is to study the expressions of COX-2, VEGF-C, and EGFR in endometrial carcinoma as well as its clinical significances. METHODS Clinical data of 183 patients with endometrial carcinoma who received surgery as initial treatment in the Nanjing Drum Tower Hospital Affiliated to the Nanjing University Medical School and the Nantong Maternal and Child Health Hospital Affiliated to the Nantong University from January 2005 to December 2010 were retrospectively investigated; 152 out of the 183 patients were closely followed up. Expressions of COX-2, VEGF-C, and EGFR proteins in 152 endometrial carcinoma samples were detected by immunohistochemical S-P assay. RESULTS A 5-year survival rate of 152 patients was 81.56% (124/152). Positive COX-2 expression rate was 67.76% (103/152), and its positive expression was related to FIGO stage, differentiation degree, and myometrial invasion depth of patients (P < 0.05), but not to lymph node metastasis (P > 0.05). Positive expression rates of VEGF-C and EGFR were 64.47% (98/152) and 82.24% (125/152), respectively, and their positive expression was associated with FIGO stage, differentiation degree, myometrial invasion depth, and lymphatic metastasis (P < 0.05). Correlation analysis on the expression of COX-2 with VEGF-C and of EGFR found that COX-2 was positively correlated with both VEGF-C and EGFR (P < 0.05, r s > 0). Patient prognosis was associated with the FIGO stage, differentiation degree, and myometrial invasion depth of tumors, as well as the presence or absence of lymph node metastasis (P < 0.05) while showing no significant association with the postoperative adjuvant therapy (P > 0.05). CONCLUSIONS COX-2, VEGF-C, and EGFR are of significance for determining the FIGO stage, differentiation degree, and myometrial invasion depth of endometrial carcinoma, of which VEGF-C and EGFR are important in determining whether tumors metastasize to lymph nodes. Combined detection of COX-2, EGFR, and VEGF-C can be used as the indices for early diagnosis, recurrence prediction, and outcome evaluation for patients with endometrial carcinoma.