Minichromosome maintenance (MCM) proteins are a group of proteins involved in DNA replication and cell-cycle regulation. Because they are associated with DNA through G1 into S phase, MCM proteins are potentially specific indicators of cell proliferation that could be valuable markers of dysplasia, and preinvasive and invasive malignant tumors. To analyze MCM protein expression patterns in actinic keratosis (AK), Bowen disease (BD), and cutaneous squamous cell carcinoma (SCC), we performed immunohistochemical staining of MCM2, -5, and -7 on tissue microarray blocks from 91 AK, 50 BD, and 174 SCC samples. The distribution and semiquantitatively assessed number of positive cells were analyzed in relation to the type of the lesion and the SCC prognostic parameters (grade, diameter, and thickness). Basal expression of all 3 proteins was observed more frequently in AK, whereas the distribution in BD was predominantly diffuse (P<0.001). All 3 proteins showed peripheral distribution in most well-differentiated SCC and diffuse distribution in poorly differentiated tumors (P<0.001). Using the 50% cut-off value, there was a statistically significant difference among AK, BD, and SCC (P<0.001). In addition, all MCM proteins showed highly significant differences (P<0.001) between well-differentiated SCC and both moderately and poorly differentiated SCC. The diffuse distribution and 50% cut-off value of positive cells revealed statistically significant associations of all MCM proteins with SCC thicker than 6 mm. Our results suggest a role for MCM proteins in the progression of in situ keratinocytic lesions and their association with high-risk features in SCC.