Serum CA125 is elevated in some endometrial cancer patients. The purpose of the present study was to assess the correlation between the presence of CA125 in endometrial cancer tissue and elevated CA125 serum levels. Serum levels of CA125 were examined in 39 patients with endometrial cancer prior to definitive surgery. After diagnosis reconfirmation, additional slides were prepared from each case for immunohistochemical staining for anti-CA125 antigens. Of the 39 patients, 28 had endometrioid endometrial carcinoma (EEC) and 11 had mixed mesodermal sarcoma (MMS). In EEC, 21.4% of the patients had an elevated CA125 serum level, and that correlated with stage (P = 0.02) but not with grade. The percentage of EEC patients with positive tissue staining was significantly higher than the percentage with elevated serum levels (89.3% vs. 21.4%, P < 0.0001). No correlation between positive tissue staining and stage or grade was observed. In MMS the percentage of positive tissue staining was also higher than that with elevated serum CA125 levels and the percentage with elevated serum levels was higher than in EEC. However, the differences were statistically not significant. Our study indicates that the majority of EEC tissues contain CA125 and that the percentage of positive CA125 tissue staining is significantly higher than that of elevated CA125 serum levels. This indicates the presence of some mechanism that prevents the access of CA125 into the circulation. This mechanism is probably less effective in more advanced EEC's and in MMS.