Aims: We aimed to investigate the immunocytoexpression profiles of a novel assay ProEx C for topoisomerase II alpha (TOP2A) and minichromosome maintenance protein 2 (MCM2) in abnormal interpreted smears. Settings and Design: Screening programs with Papanicolaou smear and high risk group human papilloma virus testing have yielded a dramatic reduction of cervical cancer incidence. However, both of these tests have limited specificity for the detection of clinically significant cervical high grade lesions. ProEx C for topoisomerase II alpha (TOP2A) and minichromosome maintenance protein 2 (MCM2) has been considered to have tight association with high grade intraepithelial lesions. Materials and Methods: A total number of 54 SurePath cervical cytology specimens of patients previously interpreted as atypical squamous cells-undetermined significance (ASC-US), atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion (ASC-H), low grade squamous intraepithelial lesion (LSIL), and high grade squamous intraepithelial lesion (HSIL) were included in our study. Results and Conclusions: ProEx C was positive in 14 of HSILs (100%), 3 of 19 LSILs (16%), 2 of 4 ASC-Hs, and none of ASC-USs (0%). The ProEx C test showed very intense nuclear staining in all cytologically abnormal cells. Further studies are indicated to evaluate the diagnostic role of ProEx C.