The distinction of complex atypical endometrial hyperplasia from endometrial adenocarcinoma is often problematic. Foci of back-to-back arrangement of glands or foci of cribriform arrangement of glands smaller than 2.1 mm in diameter are considered insufficient for the diagnosis of endometrial adenocarcinoma by some authors, and sufficient to be diagnosed as endometrial adenocarcinoma by other authors. We refer to these foci as endometrial adenocarcinoma in situ. In this study, we evaluated findings in subsequent hysterectomy in complex atypical endometrial hyperplasia patients with and without adenocarcinoma in situ. Follow-up findings, including the presence or absence of endometrial adenocarcinoma in the hysterectomy specimen, the grade of the carcinoma and the depth of myometrial invasion were analyzed. Of the total 87 patients with complex atypical endometrial hyperplasia, 33 patients had adenocarcinoma in situ and 54 lacked adenocarcinoma in situ. Of 33 patients 22 (66%) with adenocarcinoma in situ had endometrial adenocarcinoma on subsequent hysterectomy vs 13 of 54 (24%) patients without adenocarcinoma in situ (P=0.0001). Myoinvasive endometrial adenocarcinoma was present in 20 of 33 (61%) patients with adenocarcinoma in situ vs 8 of the 54 (15%) patients without adenocarcinoma in situ (P< or =0.0001). The depth of myometrial invasion in cases with myoinvasion was 24.5+19.4% in patients with adenocarcinoma in situ and 12.8+8.5% in patients without adenocarcinoma in situ (P=0.05). Among patients younger than age of 50, 5 of the 7 (71%) with adenocarcinoma in situ had myoinvasive carcinoma vs 2 of the 13 (15%) without adenocarcinoma in situ (P=0.02). The likelihood of finding endometrial adenocarcinoma in subsequent hysterectomy in patients with complex atypical endometrial hyperplasia is significantly increased if adenocarcinoma in situ is present in prior endometrial sampling. Endometrial adenocarcinomas in patients with adenocarcinoma in situ are far more frequently myoinvasive, and invade to a greater depth than endometrial adenocarcinomas seen in patients without adenocarcinoma in situ. Use of adenocarcinoma in situ terminology could lead to improved management of patients with complex atypical endometrial hyperplasia.