Taken together, we conclude that the mere genetic activation of HH/GLI signaling in epidermal cells induces profound changes within the immune microenvironment of BCC‐like lesions, thereby establishing a potent immunosuppressive milieu, which is likely to inhibit the antitumoral immune response against human BCC cells with high mutational burden. The gene discussed is GLI1; the disease is skin basal cell carcinoma.