Fifty-two cases of adenocarcinoma in situ (AIS) of the cervix uteri, or lesions closely related to AIS, have been reported by this laboratory over a five-year period. Whereas this lesion has commonly been considered a rare and usually incidental histologic finding, the large majority of these cases involved glandular atypia only and were prospectively diagnosed. Comparison of the findings from this larger series with the 11 cases of AIS described by us previously has led to a shift in emphasis from cell size to sheet architecture as the primary cytologic criterion for diagnosis of this lesion. The structure of AIS sheets was consistent with respect tothe cytologic appearances described here, even when the cells were poorly preserved. Retrospective studies of Papanicolaous smears of other cases from this laboratory that were confirmed histologically as endocervical dysplasia, microinvasive or early invasive adenocarcinoma or deeply invasive adenocarcinoma indicate that these entitites can be distinguished from AIS primarily on the basis of the architecture of the sheets of cells. Cellular groups comprising small, crowded nuclei were a feature of several undercalled deeply invasive adenocarcinomas, and the diagnostic significance of this material is discussed.