The present study underscores the distinct differences in the cutaneous squamous cell cancer (cSCC) susceptibility and progression among the four murine models (SKH-hr1, SKH-hr2, SKH-hr2+ApoE, and Nude), with the Nude, SKH-hr2 and SKH-hr2+ApoE mice demonstrating a higher propensity for papilloma and tumor development, influenced by both genetic factors and UV radiation, while the SKH-hr2 and SKH-hr2+ApoE models seem to exhibit the phenomenon with greater intensity. Here, APOE is linked to papilloma.