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Penile carcinomas are infrequent in the USA and Europe, but fairly frequent in some geographical regions of Asia, Africa, and Latin America. The vast majority of tumors are squamous cell carcinoma, which disseminate in a loco regional manner to intrapenile anatomical structures: lamina propria, corpus spongiosum, and corpus cavernosum in the glans and lamina propria, dartos, and outer skin in the prepuce. Nodal spread is in the sentinel, superficial, and deep groin nodes, and then to pelvic or iliac lymph nodes. Widespread dissemination occurs in a third of the cases, usually in locally advanced disease. Pathologic factors important to predict regional metastasis and patient's outcome are: site and size of the primary tumor, growth pattern, histologic grade, subtype of squamous cell carcinoma, tumor depth of invasion, and the prognostic index. Tumors in the foreskin have a better prognosis because they are of lower grade and more superficial than those of the glans. Neoplasms with superficially spreading, multicentric, or verruciform patterns of growth carry a better prognosis than those of a vertical growth. There is a correlation between high histologic grade, deep intrapenile invasion, and nodal metastasis in penile squamous cell carcinomas. Superficially invasive tumors in the lamina propria, corpus spongiosum, or dartos tend not to be associated with metastasis whereas those deeply invasive in the corpus cavernosum, in the glans, or skin of the foreskin are associated with a high risk of metastasis. Considering the variability in the gross presentation of penile neoplasms, which make the use of a single measurement system difficult, we describe 3 methods to evaluate the depth of invasion: tumor depth (for smaller tumors—measured from the basement membrane of the adjacent uninvolved epithelium to the deepest point of tumor invasion), tumor thickness (for bulky or verruciform tumors—measured from the granular layer of the tumor to the deepest point), and anatomical levels of invasion (for all tumors. In the glans, the levels are lamina propria, corpus spongiosum, and corpus cavernosum; in the foreskin, the levels are lamina propria, dartos, and skin). The histologic subtype of squamous cell carcinoma associated with almost no risk of metastasis is the pure verrucous carcinoma. A mixed component should be ruled out by submitting multiple sections of the tumor. Low risk for metastasis is found in papillary NOS (not otherwise specified) and warty (condylomatous) carcinomas. Basaloid and sarcomatoid carcinomas are associated with higher risk of nodal metastasis. Vascular invasion is a more important predictor of metastasis than perineural invasion. The prognostic index is a system we use in our practice to predict metastasis and survival. It is represented by numbers 1 to 6, arrived at by adding numerical values given to histologic grades (1-3) and to anatomical levels of invasion (1-3) in the glans and foreskin. Low indexes (1-4) are associated with low metastatic rate. The use of prognostic molecular markers is not yet a common practice in the pathologic and clinical management of penile cancer.