Between 1986 and 1996, 263 patients, 156 females and 107 males, affected by oral lichen planus (OLP), were followed at the Division of Oral Medicine and Pathology, University of Naples 'Federico II', Italy, and at the Institute of Dentistry and Maxillofacial Surgery, University of Bari, Italy. During this follow-up, the possible association of OLP with oral squamous cell carcinoma (SCC), together with the possible association of OLP, oral SCC and chronic HCV-hepatitis, were investigated. 14 cases (5.32%) were known to have developed oral SCC: 10 (3.8%) in an area of pre-existing OLP, 3 (1.14%) in other sites, in 1 case the diagnosis of OLP and SCC was synchronous (0.38%). 3 patients were positive for anti-HCV antibody. Many carcinomas were in areas of reticular/plaque OLP. 3 patients had multiple simultaneous sites of oral involvement (21.42%); 5 patients developed oral SCC in different sites during the follow-up period (35.71%). These data, together with a clear histological evidence of progression to carcinoma within OLP lesions, suggest the probability of some cases of at least OLP having an intrinsic property predisposing to neoplastic transformation, confirming previous studies. For these reasons, the authors think that it is necessary to follow-up the patients regularly at least annually and possibly for life for the early diagnosis of a possible neoplastic degeneration. These consideration are particularly important in the case of atrophic or erosive OLP, and plaque OLP, especially when involving the dorsum of tongue.