Objective. To evaluate the therapeutic regimens and symptomatic response rates in patients with vulvar lichen sclerosus associated with variable degrees of squamous cell hyperplasia (mixed disease). Material and methods. Eighty-three women with biopsy-proven vulvar mixed disease were evaluated for this retrospective study. All patients were initially treated with topical fluorinated corticosteroids, and then 2% testosterone propionate in petrolatum or 0.05% clobetasol 17-propionate (44 (53%) versus 39 (47%)). Results. The remission rates were 82 and 93% in the testosterone and clobetasol subgroups at the end of 6 months (p = 0.112), respectively. The disease recurred in 8% of the patients. The recurrence rates in the testosterone and clobetasol arms were 13 and 5%, respectively (p = 0.163). The histopathological review of the repeat vulvar biopsies of the patients without symptomatic relief revealed 6 (60%) patients with persistent disease, 2 (20%) with lichen sclerosus, 1 (10%) with atypical squamous hyperplasia, and 1 (10%) with VIN 1. Two patients with recurrent disease and 2 patients with vulvar intraepithelial neoplasia I-II or atypical squamous hyperplasia were treated with skinning vulvectomy. Conclusions. Clobetasol resulted in higher remission and lower recurrence rates than those in testosterone therapy, although statistically significant differences were not obtained. In the evaluation of patients without symptomatic relief, the first step should be a vulvar biopsy to exclude the presence of atypical components.