Reactive and regenerative squamous epithelium can show a spectrum of histologic alterations that mimic dysplastic and pre-neoplastic cytological and architectural changes. A monoclonal antibody cocktail targeted against mini-chromosome maintenance protein 2 (MCM2) and DNA topoisomerase IIA (TOP2A), when up regulated, serves as a marker of aberrant S-phase induction in proliferating cells (1). MCM2 functions during DNA replication by loading the pre-replication complex onto DNA and unwinding the DNA through helicase activity to permit DNA synthesis. MCM2 is essential for eukaryotic DNA replication and drives the formation of prereplicative complexes, which is the key first step during G1 phase (2). Therefore, altered MCM2 expression may be a hallmark of cell-cycle deregulation, which could be the most essential mechanism in the development and progression of human cancers (2). This protein is overexpressed in cervical dysplasia as a result of HPV infection and subsequent uncontrolled activation of gene transcription and aberrant S-phase induction, which is mediated through the E2F transcription factor pathway. The overexpression of MCM2 provides the link between oncogenic HPV infection and the molecular event of cervical dysplasia (3,4). It has been shown that over-expression of MCM2 in cervical high grade dysplasia can be detected by immunohistochemistry (2). TOP2A is a nucleic enzyme that affects the topological structure of DNA by interacting with the double-helix DNA, thus playing an important role in DNA replication, transcription, recombination, condensation, and segregation (5,6). A monoclonal antibody cocktail directed against MCM2 and TOP2A is a novel immunostaining marker that has been tested in liquid-based cervical cytologic smears and cervical biopsy specimens as a potential diagnostic adjunct for the detection of high grade intraepithelial neoplasia and low grade intraepithelial neoplasia (7,8).