Nucleolar protein p120 is a proliferation-associated antigen expressed by cells in early G1 phase, identified by the monoclonal antibody FB-2. Its expression has been evaluated in breast and prostate cancer, and proved to be significantly correlated with other prognostic parameters. In oral pathology, p120 protein content is able to distinguish between non-neoplastic and malignant lesions. In the present study, the immunohistochemical expression of p120 protein was evaluated in fifty cases of oral squamous carcinoma and compared with histological grading, pTNM staging, DNA ploidy status and follow-up of the patients, in order to establish its prognostic value, p120 mean area was significantly correlated to all these parameters, apart from lymph node involvement, indicating the strong predictive potential of this marker. In conclusion, quantitative immunohistochemical analysis of p120 protein represents an easy and reliable method for the assessment of clinical outcome and the definition of risk groups in oral carcinoma.