Buschke-Lowenstein Tumor (BLT) is a very rare sexually- transmitted disease associated with human papillomavirus type 6 and 11, but rare cases of oncogenic HPV types including HPV 16 and HPV 18 were also reported. BLT is located in the genital, anorectal and perianal regions. It is regarded as a type of verrucous carcinoma occurring on anogenital mucosal surfaces where it is locally invasive but displays a benign cytology. Buschke-Lowenstein tumor can be associated with a high rate of recurrence and a risk of malignant transformation to invasive SCC, especially in patients with oncogenic types of HPV. We report the case of a 59-year-old female patient who addressed our clinic for a large, exophytic, cauliflower-like tumor involving the vulva, perineum and perianal regions with 20 years duration. The first lesions had been appeared on vulva and after 3 years period they grown slowly and covered perineum and perianal area. They had cauliflower like surface, with different sizes. In some points erosions and yellowish secretion with odor are observed. Histologic examination of a biopsy specimen of large tumor presented nets of well- differentiated squamous cell carcinoma, as well as a marked mononuclear cell infiltrate and conspicuous koilocytosis. HPV DNA for 6 and 11 types was detected with PCR. The patient was sent to the gynecology surgery department for excision and remains under the supervision of the dermatology and oncology department for rapid treatment of relapses and early detection of malignant transformation.