Since squamous cell carcinoma of the penis is rare, prospective trials do not exist. Therefore, new treatment strategies have to be developed. Based on our experience with the treatment of 22 patients with penile squamous cell carcinoma, we describe our therapeutic approaches. Ten patients with superficial disease (T1-2N0M0) were treated with partial penectomy. The 3-year survival rate amounted to 90%. In patients with extensive disease (T3-4 or N1-3) a partial or total penectomy was performed. After initial antibiotic therapy for 4 weeks, patients underwent inguinal lymph-node dissection and if the nodes were positive, additional pelvic lymph-node dissection. In patients with ulcerous inguinal lymph-node metastases surgical resection was performed, covering the wound with a musculocutaneous flap (tensor fascia lata flap n = 2; rectus abdominis flap n = 1). The 3-year survival rate of patients with T1-2N1 tumours (n = 4) was 67% and with T3-4N1-3 (n = 8) 25%. Patients with distant metastases received inductive systemic chemotherapy with cisplatin, methotrexate and bleomycin. Objective responses occurred in 22% (1 CR, 1 PR) of 9 patients. These results suggest that immediate radical surgery with lymph-node dissection is the best treatment for squamous cell carcinoma of the penis.