Hence, these findings implicate a crucial role of lymphangiogenesis and EMT of Paget cells in promoting LN metastasis of EMPD, and blocking the CXCR4–SDF-1 axis can be a novel option of adjuvant therapy for patients with CXCR4-positive invasive EMPD to prevent LN metastasis. Here, CXCR4 is linked to extramammary Paget disease.