Laryngeal keratosis (LK) is a precancerous mucosal change with a variable possibility of malignant transformation. Recent studies evidencing HPV-DNA genomes in a large series of non-malignant and malignant laryngeal lesions suggest a role of HPV in the transformation of laryngeal lesions possibly in synergistic interaction with other carcinogens. In this study, we analyzed 115 biopsy specimens from benign laryngeal lesions to evaluate the risk of malignant transformation and its relationship to degree of dysplasia and to histological features of virus cell infection. The rate of transformation of LK was 8% (9/115). Our results indicate that the risk of transformation in laryngeal keratoses without dysplasia (LKWOD) is lower than that in laryngeal keratoses with dysplasia (2.2% vs 25%, respectively) (p < 0.05). An increased risk of malignant evolution in laryngeal keratoses with dysplasia (LKWD) was also related to the degree of dysplasia (rate of transformation of 12.5, 22.2 and 36% in mild, moderate and severe dysplasia, respectively). Histological features suggesting HPV infection (koilocytic-like atypia and epithelial papillary hyperplasia) were found in 6 LK only, no case subsequently developing cancer. In both benign and transformed LK, analyzed by ISH, we failed to detect HPV genomes, suggesting a major role of others carcinogens, such as tobacco and/or alcohol, in the transformation of LK.