Surgeons often perform small or superficial penile biopsies that are difficult to classify definitely with regard to a benign or malignant nature, and if malignant, cannot always be accurately subclassified. Staging and therapeutic decisions rely on the identification, in these materials, of pathologic parameters related to prognosis. In this study, we evaluated the accuracy and completeness of pathologic information obtained from biopsies of 57 consecutive patients with squamous cell carcinoma (SSC) of the penis, and compared it with the information obtained from penectomies. Diagnostic accuracy was determined by recording discordances of critical factors in biopsies and penectomies. The evaluated parameters were as follows: cancer diagnosis, histologic type, tumor grade, depth of invasion (anatomical levels), and vascular invasion. Histologic subtypes of SCC were the following: usual 37, verruciform 11, mixed 7, pseudohyperplastic 1, and sarcomatoid 1. Grades were 1, 2, and 3 (well, moderately and poorly differentiated). Levels of invasion were lamina propria, corpus spongiosum, and corpus cavernosum in the glans; and lamina propria, dartos, and skin in the foreskin. In 2 patients with well-differentiated tumors a diagnosis of cancer could not be established in biopsy material. In 17 cases (30%) there was a biopsy-penectomy discordance of histologic types, especially of verruciform and mixed carcinomas. Biopsies failed to identify the correct histologic grade in 30% of the cases. A higher grade was usually identified in penectomy specimens. Because biopsies were superficial, the deepest point of invasion could not be determined in 91% of the cases. Vascular invasion was identified in biopsies in only 1 of 8 patients. In summary, biopsies were useful for cancer diagnosis except in 2 differentiated variants of penile squamous cell carcinoma. However, important pathologic parameters related to prognosis were missed on biopsy materials, and they were more accurately evaluated in penectomy specimens. We conclude that clinical and pathologic staging of penile cancer, at least in our material, cannot depend on biopsy information alone. Data from biopsies may be insufficient to make a decision whether to perform a groin dissection, or for prognostic evaluation in those patients in whom other treatment modalities (such as radiotherapy or chemotherapy) are being considered.