Squamous cell carcinoma (SCC) of the penis is a rare disease, representing 0.4% to 0.6% of all malignant neoplasms among men in the United States and Europe. In 2017, the estimated number of new cases of penile and other male genital cancers in the United States is 2120, with 360 predicted cancer-specific deaths. Incidence is higher (up to 10%) among men in the developing countries of Asia, Africa, and South America. The most common age of presentation is between 50 and 70 years. Early diagnosis is of utmost importance, as this is a disease that can result in devastating disfigurement and has a 5-year survival rate of approximately 50% (over 85% for patients with negative lymph nodes and 29%–40% for patients with positive nodes, with the lowest survival rates at 0% for patients with pelvic lymph node [PLN] involvement). As the rarity of this disease makes it difficult to perform prospective, randomized trials, the NCCN Panel relied on the experience of penile cancer experts and the best currently available evidence-based data to collectively lay down a foundation to help standardize the management of this malignancy.