Penile squamous cell carcinoma (SCC) is considered a loco-regional disease with a fairly predictable pattern of progression. Widespread dissemination occurs in at least one-third of the patients. Local recurrence (defined as the presence of tumor after a primary treatment affecting any remainder tissue, including skin, erectile corpora, or urethra) present in up to 30% of the patients increases the risk of regional inguinal and pelvic lymph nodes metastases. The aim of this study was to identify adverse pathologic prognostic factors in patients with recurrent tumors. Clinicopathologic features of 81 surgically treated patients (25 with recurrent and 56 with nonrecurrent SCC) were evaluated; 56 patients (19 with recurrent and 37 with nonrecurrent tumors) additionally received groin dissections. Follow-up (2 to 372 mo, mean of 71 mo) was obtained in all patients. Comparison of recurrent tumors at the time of the primary diagnosis and of recurrence showed that histologic subtype and grade were identical in 76% of the cases and converted to a higher grade tumor in 24% of the cases, especially, in patients treated with local excisions and circumcisions. Most of the recurrences (67%) seemed at or before 12 months. Comparison of recurrent and nonrecurrent tumors showed that high grade tumors (basaloid and sarcomatoid) tended to be significantly associated with recurrent tumors, whereas low grade variants (papillary, warty and verrucous) were more frequent in the nonrecurrent group; recurrent tumors invaded into deeper anatomic levels than nonrecurrent tumors. The incidence of inguinal lymph node metastasis was higher in recurrent tumors (79% vs. 49%, P=0.0272). Cancer-specific survival was of 46% versus 76% at 3 years of follow-up in recurrent and nonrecurrent tumors, respectively. Patients with recurrent tumors had a median survival of 2.9 years; no major changes in survival were noted after 3 years of follow-up. Mortality was higher in the recurrent group (56% vs. 29%, P=0.0188); 80% of patients with high-grade tumors (basaloid, sarcomatoid, and high grade usual or hybrid verrucous SCCs) died from penile cancer. Mortality in patients with usual SCC was higher in the recurrent group, but similar in basaloid and sarcomatoid SCCs. After 3 years there was no survival difference in patients with low-grade recurrent tumors; however, in the high grade recurrent group there was a progressive and gradual decrease in survival from 2 to 10 years (median survival of 2.5 y). In summary, histologic subtypes and grades of SCCs were similar in the majority of original and recurrent carcinomas. Inguinal metastasis and mortality were higher in recurrent than in nonrecurrent carcinomas. Basaloid, sarcomatoid, and mixed usual-verrucous variants and invasion of corpora cavernosa or preputial skin were significant adverse prognostic factors of recurrent carcinomas. Local excision and partial penectomy were not adequate procedures for sarcomatoid and basaloid penile carcinomas. Carcinomas of foreskin had a better prognosis. Conversion from low to high-grade carcinoma was related to significant mortality. The identification of the adverse prognostic factors found in this study should be the base for an aggressive initial therapy to prevent recurrence in a subset of penile cancers. Re-excision of the recurrent tumor permitted the control of the disease only in one-third of the patients.