A new tumor-associated antigen, MN, has been identified whose expression correlates with the tumorigenic phenotype of HeLa x fibroblast somatic cell hybrids. Because HeLa is a cell line derived from a cervical carcinoma, we investigated the diagnostic utility of MN expression in cervical neoplasia. It was found that normal cervical tissue does not express the antigen, or does so in occasional focal areas of weakly staining reserve cells. In contrast, significant immunoreactivity (immunoperoxidase staining of paraffin-embedded sections) was observed in cervical intraepithelial neoplasias, adenocarcinoma in situ, and frank carcinomas, both squamous cell and adenocarcinoma. Varying patterns of immunoreactivity were observed and were characterized as diffuse, diffuse/focal, or focal. Greater than 90% of dysplastic or malignant tissues showed immunoreactivity. An interesting observation was that normal cervical tissue associated with cervical intraepithelial neoplasias, or adenocarcinoma in situ showed a staining pattern in the reserve cells and/or normal columnar cells that approximated the level of intensity exhibited by the dysplastic tissue. These results indicate that MN antigen expression has potential utility as a biomarker of cervical neoplasms.