One hundred cases were studied in detail using lymphangiograms (LAG), anatomic dissections, and/or microscopic evaluation. LAG performed via the dorsal lymphatics of the penis demonstrate the existence of specific lymph node center, the so-called sentinel lymph node (SLN). This appears to be the primary site of metastases from penile carcinoma. The SLN is visualized radiographically, on the antero-posterior view, at the junction of the femoral head and the ascending ramus of the pubis. Anatomically, the SLN is part of the lymphatic system around the superficial epigastric vein. Forty-six SLN biopsies were performed with 15 positive for metastatic disease. In these 15 patients, an inguinofemoroiliac dissection was performed; in 12 cases there was no involvement of other lymph nodes. Lymphatic channels draining into the iliac lymph nodes without first draining into the sentinel lymph node were never demonstrated, nor were the inguinal-femoral lymph nodes involved in the absence of SLN involvement. On this bases, we recommend preliminary bilateral SLN biopsy to be followed by inguinofemoroiliac dissection when biopsy of the SLN biopsy to be followed by inguinofemoroiliac dissection when biopsy of the SLN is positive. When biopsy of the SLN is negative for metastatic disease, no further surgical therapy is immediately indicated. With negative SLN, 5-year survival was 90%. When SLN alone was involved, 5-year survival was 70%. Five-year survival was 50% with both SLN and other inguinal nodes involved. When iliac metastases were also present, 3-year survival was 20%.