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In order of frequency, cervical intraepithelial neoplasia (CIN), combined adenocarcinoma in situ (AIS)/CIN lesions, and solitary AIS are the most prevalent premalignant lesions of the uterine cervix. As the morphologic distinction of these subtypes is not always straightforward, we performed an immunophenotyping analysis to establish distinguishing profiles for each of these squamous and glandular progenitor lesions of cervical carcinoma. A series of 26 premalignant cervical lesions, comprising 13 cases of AIS, of which 7 represented solitary AIS and 6 were combined with CIN (combined AIS/CIN), as well as 13 solitary high-grade CIN lesions, were immunophenotypically analyzed using antibodies directed against p16, p63, bcl-2, and cytokeratins (CK) 5, 7, 8, 13, 17, 18, and 19. Adjacent normal epithelia were also investigated. CIN lesions expressed the full panel of antibodies. Combined AIS/CIN lesions also expressed the full complement of markers in both the AIS and CIN compartments. However, the expression of p63, bcl-2, CK5, and CK17 was lower in AIS compared with CIN. The solitary AIS lesions could be subdivided into 2 subgroups, 1 expressing the full complement of markers and a second group in which no expression of p63, bcl-2, CK5, and a sporadically CK17 expression was observed. We conclude that 2 phenotypically distinct types of AIS can be identified, that is, AIS with a reserve cell marker phenotype and AIS with an endocervical glandular phenotype. These observations support the view that reserve cells are capable of bidirectional premalignant transformation, that is, into CIN and reserve cell-type AIS, as well as combined AIS/CIN. The endocervical type of AIS is probably a result of the unidirectional transformation of progenitor cells within the glandular cell compartment.