Background: Preoperative diagnosis of adenomyosis and uterine myoma can be aided by pelvic ultrasonography and cancer antigen 125 (CA125). Objective: This study aimed to evaluate the usefulness of CA125 level and transvaginal ultrasonography in diagnosis of uterine myoma and adenomyosis and to differentiate both lesion. Patients and Methods: One hundred patients complaining of abnormal uterine bleeding were included in this study. They were attending the Obstetrics and Gynecology Departments at Zagazig University Hospitals and Al-Ahrar Teaching Hospital for hysterectomy. Transvaginal ultrasonography (TVS) was done for all selected cases to examine the pelvis for detecting any pathology. CA 125 level was measured. Hysterectomy specimens were histopathologically examined. Results: The combination of serum CA125 level and TVS showed that it was useful in adenomyosis group as CA125 level increased the accuracy of TVS from 77% to 80.2%, while in myoma group the combination was not useful as CA 125 decreased the accuracy of TVS from 100% to 83.3%. Conclusion: Transvaginal ultrasonography is the most sensitive for myoma (100%) & CA125 level is the most specific (77%) for adenomyosis. CA125 level had the highest sensitivity (87.5%) for adenomyosis than transvaginal ultrasonography (80.1%). Combining both TVS and CA125 level increased the accuracy for detection of adenomyosis to 80.2% but decreased it to 83.3% in detection of uterine myoma.