The use of endocervical brushes has led to a generous sampling of both endocervical and "lower uterine segment" (LUS) cells. To an unfamiliar eye, the large fragments of endometrial tissue from the LUS may lead to misinterpretation as endometriosis or glandular malignancy, as happened in our institution when the use of endocervical brush and recognition of LUS cells in cervical smears were limited. Eight cases, cytologically interpreted as such, were proven to be benign following cervical biopsy or endometrial curettage. The nature of LUS cells was recognized only on retrospective review of this cytologic material. However, in recent years, routine use of the endocervical brush resulted in an influx of similar cases referred by the cytotechnologists to the pathologist as glandular atypia. Thus, to get familiarized with the cytomorphology of LUS cells and its diagnostic pitfalls, a prospective study was undertaken. This entailed a review of 62,187 consecutive cervicovaginal smears (women of post-hysterectomy status were excluded) received within a 12-mo period (July 1, 1992-June 30, 1993). A total of 344 smears (0.55%) showed large tissue fragments of branching tubular endometrial glands with and without surrounding stroma. Patients ranged from 14-82 yr of age. History of cervical cone biopsy was noted in nine patients (2.6%). Repeat cervical smear or concurrent endometrial or endocervical biopsy available in 84 patients (24.4%) were negative. LUS cells may be mistaken for endometriosis, epithelial glandular atypia, as well as carcinoma of both endocervical and endometrial origin. In addition to glandular abnormality, LUS cells may also be misinterpreted as that of squamous intraepithelial lesion.(ABSTRACT TRUNCATED AT 250 WORDS)