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Giant condyloma acuminatum (GCA) is a rare cauliflower-like lesion, also known as Buschke-L ewenstein tumor (BLT). Although characterized by benign histological features, the local behavior of GCA is extremely aggressive, showing progressive infiltration of the surrounding structures leading to tissue destruction by compression. As the correlation between HPV and GCA development grew stronger, the majority of the Authors came to the conclusion that HPV can not only cause CA but, associated with particular risk factors, it can lead to much more serious conditions such as BLT. Since the treatment of GCA is still not yet standardized, a very accurate pre-operative analysis of the lesions is required to plan the most suitable treatment approach. Based on current knowledge, macroscopic evaluation of local tumor invasion and extensive radical resection appear to be the only valid therapeutic approach, due to its association with longterm survival and minimal recurrence. Looking forward for new techniques and new tissue sparing treatments, at the moment, GCA can be safely treated with radical excision without immediate tissue reconstruction; long-term complications, such as stricture and stenosis, can be prevented by adequate wound healing and by a particularly intense and long- term follow-up program.