INTRODUCTION: Penile cancer is a rare malignancy, and few guidelines are available to define treatment paradigms. For greater understanding of the natural history of surgically treated penile cancer, we analyzed the experience at our institution. MATERIALS AND METHODS: Using an institutional database, we identified 127 patients treated for squamous cell carcinoma of the penis from 1995-2011. Cancer-specific survival (CSS) was calculated using the Kaplan-Meier method. Survival data were compared using the log-rank test. The difference in risk of cancer-specific death by lymph node status and histological grade was determined by univariate Cox regression analysis. RESULTS: Five year CSS for pTis, pT1, pT2, and pT3/4 was 100%, 84% (95% CI 58%-95%), 54% (95% CI 33%-71%), and 54% (95% CI 25%-76%), respectively (p â¤ .005). Three year CSS for patients with N0, N+, and Nx disease was 90% (95% CI 47%-99%), 65% (95% CI 47%-79%), and 86% (95% CI 73%-93%), respectively (p = .03). The receipt of neoadjuvant chemotherapy did not change per 5 year period over the 16 years of our study. Median follow up was 2.8 years. CONCLUSIONS: Penile cancer patients with advanced disease had poor survival. Tumor stage and nodal status were significant predictors of CSS. Penis-sparing approaches may be considered for most patients; however, pathological stage and grade dictate the management and ultimate outcome. Further studies are necessary to clarify the benefits of chemotherapy in this disease.