BACKGROUND We present our initial experience with the use of the squamous cell carcinoma (SCC) antigen (SCCAg) in 16 men with penile SCC (SCC group), in four men with condyloma acuminatum (benign group), and in 32 blood donors (control group). METHODS The SCCAg levels were measured at presentation and every 6 months (upper limit was 2 ng/mL). The mean follow-up time was 4 years. RESULTS All non-SCC patients had normal SSCAg serum levels in contrast with the SCC patients. The presence of nodal and/or distant metastases resulted in statistically significant higher SCCAg levels, both at presentation and during the follow-up. In patients undergoing lymph node dissection with elevated SCCAg levels prior to the procedure, there was a statistically significant decrease of the SCCAg levels after the operation. CONCLUSION The SCCAg level could be a serum marker that holds promise for clinical use in penile SCC. Sequential monitoring of SCCAg level might indicate developing of nodal and/or distant metastases and could be useful in following the response to treatment.