Background:The objective of this study was to assess mast cells and TNF-α in oral lichen planus (OLP) and oral lichenoid reactions (OLR) patients as diagnostic marker to the differential diagnosis of OLP and OLR diseases.Materials and Methods:In this cross-sectional study, samples were obtained from 30 OLP and 30 OLR patients, between June 2010 and March 2011 in Dental clinic of the University of Isfahan, Iran. Mast cells in the reticular layer of the lamina propria for samples were evaluated using toluidine blue method and immunohistochemical technique. The clinical relevant data taken into account were: demographical data, total number and degranulated mast cells, ratio of degranulated mast cells and TNF-α positive degranulated mast cells.Results:In OLP and OLR, the total mast cells were 21.2 ± 7.9 and 20.3 ± 6.8, degranulated mast cells were 15.5 ± 6.9 and 19.2 ± 6.9, ratio of degranulated mast cells to total mast cells were 0.716 ± 0.067 and 0.946 ± 0.081, and TNF-α positive degranulated mast cells were 13.6 ± 6.3 and 17.1 ± 6.04, respectively. There was no significant difference for the total mast cells. But degranulated mast cells, ratio of degranulated mast cells and TNF-α positive degranulated mast cells in OLR were significantly higher than OLP patients.Conclusions:Our results showed that the degranulated mast cells, ratio of degranulated mast cells and TNF-α in OLR was significantly more than OLP patients and these may be able to be used as diagnostic markers to the differential diagnosis of OLP and OLR.