Herein, we studied a cohort of high risk cSCC patients and found that PNI cSCC was associated with increased expression of MAGE-A3 and cyclins E, A and B. We also found that elevated mRNA levels of collagen XI and matrix metalloproteases 3, 10, 11, and 13 were observed in poorly differentiated cutaneous squamous cell carcinoma with PNI. Here, MAGEA3 is linked to skin squamous cell carcinoma.