Usage of liquid-based cytology has resulted in better cellular preservation with enhancement of nuclear features. The purpose of this retrospective 2-yr study (January 1999 through December 2000) was to evaluate the cellular features of endocervical gland involvement by a high-grade squamous intraepithelial lesion (HSIL) vs. endocervical adenocarcinoma in situ (AIS) on cell samples processed by the ThinPrep method as compared to conventional smears. Of the 97 cases of CIN III diagnosed on cytology, 52 (54%) showed surface endocervical gland involvement by CIN III and form the basis of this study. There were also six cases of endocervical AIS diagnosed on histology with prior cytology. The architectural features of HSIL involving endocervical glands and AIS were similar to those previously reported on conventional smears. A consistent finding of HSIL involving endocervical glands was the loss of central cell polarity and piling within cell groups, a finding not present in AIS. Central cell polarity was maintained in cellular groupings of AIS. In addition to the cellular feature present on conventional smears, micronucleoli were clearly visualized in cells of HSIL involving endocervical glands and prominent nucleoli were present in AIS. Apoptosis and mitoses were clearly visualized in both entities. Endocervical gland involvement by HSIL has characteristic cell patterns and features on liquid-based/thin-layer cytology that permit their distinction from AIS.