Giant condyloma acuminatum (GCA), also known as the Buschke-Löwenstein tumor (BLT), is a rare, locally aggressive lesion of the anogenital region caused by human papillomavirus (HPV) infection, with potential for malignant transformation and a high recurrence rate after treatment. We report the case of a 47-year-old multiparous woman with a seven-year history of an untreated, slow-growing perineal lesion that ulcerated and began to bleed actively seven months before presentation. Physical examination revealed an extensive exophytic, cauliflower-like lesion extending from the perineum to both gluteal regions, the sacrum, and the vaginal introitus, measuring approximately 20 × 15 cm. Serologic testing for HIV, syphilis, and hepatitis was negative. An incisional biopsy confirmed HPV-associated condyloma acuminatum without malignancy. Given the extent of disease and its proximity to the anal sphincter complex, the case was discussed in a multidisciplinary tumor board, and neoadjuvant radiotherapy (50 Gy in 25 fractions) was administered, achieving a partial response with more than 50% reduction in lesion size. Wide surgical resection with electrofulguration was subsequently performed; intraoperative findings showed infiltration of the anal sphincter, levator ani, and anococcygeal ligament. The final specimen showed macroscopically positive margins but no histologic evidence of malignant transformation. The patient had a favorable postoperative course, with wounds healing by secondary intention, and received adjuvant nonavalent HPV vaccination one month after surgery. This case illustrates the value of a multidisciplinary, organ- and function-preserving approach combining neoadjuvant radiotherapy and surgery in the management of giant anogenital condylomas, and highlights the potential role of adjuvant HPV vaccination in this setting.