Objective To compare the ability of transvaginal sonography and serum CA 125 levels to predict myometrial invasion in patients with endometrial carcinoma. Design and methods Prospective study in 50 consecutive patients (mean age 60 years, SD 10.5, range 29-77 years) diagnosed as having endometrial cancer and scheduled for surgical staging. All patients were evaluated by transvaginal ultrasonography. Endometrial thickness was measured in all cases and myometrial invasion was estimated as <50% or greater than or equal to 50%. Serum CA 125 level was determined in each patient. A cut-off level of greater than or equal to 35 IU/ml wits considered to predict myometrial invasion of greater than or equal to 50%. All patients underwent surgical staging, and definitive histopathological findings regarding myometrial invasion were used as the 'gold standard'. Sensitivity, specificity and positive predictive value (PPV) and negative predictive value (NPV) were calculated for transvaginal ultrasonography and CA 125 and compared. Results On histopathological analysis, myometrial invasion was found to be <50% in 35 (70%) cases and greater than or equal to 50% in 15 cases (30%). Mean endometrial thickness in patients with superficial invasion was significantly tower than in those with deep invasion (13.4 mm (95% CI 11.2-15.7) vs. 18.7 mm (95% CI 15.0-22.3), respectively; p = 0.014). Median CA 125 runs significantly higher in patients with deep invasion than in those with superficial invasion (30 IU/ml, interquartile range (IQR) 46.0 vs. 16.9 IU/ml, IQR 13.9, respectively; p = 0.002. The sensitivity, specificity, PPV and NPV for transvaginal ultrasonography were 86.7% (95% CI 59.5-98.3), 94.3% (95% CI 80.8-99.3), 86.7% (95% CI 59.5-98.3) and 94.3% (95% CI 80.8-99.3), respectively. The sensitivity, specificity, PPV and NPV for CA 125 were 40% (95% CI 16.3-67.7), 91.4% (95% CI 76.9-98.2), 66.7% (95% CI 29.9-92.5) and 78% (95% CI 63.4-89.5), respectively. The sensitivity of transvaginal ultrasonography was significantly higher than that of CA 125 (p = 0.008). No differences were found in terms of specificity, PPV or NPV. Conclusion Our results indicate that transvaginal ultrasonography is more sensitive than CA 125 in predicting myometrial invasion in endometrial cancer.