The most important complication of oral lichen planus (OLP) is the development of oral squamous cell carcinoma (OSCC) but this is a very controversial matter. The aim of the study was to estimate in a Northern Italian cohort of OLP patients the risk for OSCC. Four hundred and two patients with histologically confirmed OLP diagnosed from January 1988 to July 1999, were followed-up to the end of February 2001. The standardized incidence ratio (SIR) of OSCC was calculated for the entire cohort and specific for gender, type of OLP, therapy for OLP and hepatitis C virus (HCV) infection. The relative risk (RR) of OSCC according to HCV infection was also estimated in the cohort. During the follow-up period, two men (1.3%) and seven women (2.9%) developed an OSCC. The SIR was 44.9 (95% CI: 20.5-85.2), being higher among women, but statistically significant in both genders. The RR of OSCC for patients with HCV as compared with those without HCV infection was 3.16 (0.8-12.5). Patients with OLP had a significantly increased risk of OSCC, irrespective of the clinical type of OLP and therapy. HCV infection apparently increased the risk for OSCC although this result could reflect the role of confounders, such as liver cirrhosis.