The reported prevalence rate of anti-hepatitis C virus (HCV) antibodies in patients with oral lichen planus shows wide geographical variation and ranges from 0 to 65%. Certain characteristic clinical features have been attributed to oral lichen planus associated to HCV infection. The purpose of this investigation has been to assess hypothetical clinical differences, as well as differences in the intensity of the subepithelial inflammatory infiltrate between oral lichen planus-HCV +ve patients and oral lichen planus-HCV -ve patients. A total of sixty-two patients entered the study. Their mean age was 63.5 +/- 14.49 years, and 48.4% of them were men and 51.6% women. Patients were classified according to their serum HCV positivity. Age, sex, clinical presentation (reticular or atrophic-erosive), extension of the lesions, location of the lesions, number of locations affected, intensity of the inflammatory infiltrate and Candida albicans colonization were recorded for each patient. Reticular lichen planus was the most frequent clinical presentation in both HCV +ve (57.1%) and HCV -ve patients (63.6%). C. albicans colonization ranged from 42.8% in HCV +ve and 41.7% in HCV -ve patients. HCV + ve patients showed certain oral locations more frequently affected than HCV -ve ones: lip mucosa, 28.6% versus 7.3%; tongue, 57.1% versus 29.1%; and gingiva, 71.4% versus 23.6%. The number of affected intraoral locations was higher in HCV +ve patients (71.4%) than among HCV -ve ones (20.4%; chi2 = 8.34; P < 0.011). No statistically significant differences could be established in terms of density of subepithelial inflammatory infiltrate between the groups. Our results reinforce the need for liver examination in all patients with oral lichen planus, particularly those showing lesions on the gingiva with multiple intraoral locations affected, as no pathological differences could be identified between HCV + ve and HCV -ve patients.