The expression of p16 INK4A has been investigated in oral leukoplakias (OLK), but no data are available about oral lichen planus (OLP). In this study, p16 INK4A immunohistochemical expression was evaluated in 56 OLP and 36 OLK (12 without inflammation [NI-OLK] and 24 with chronic inflammation [I-OLK]) and compared with 23 reactive nonspecific inflammations (INF) and 14 normal control samples. The p16 INK4A immunostaining was considered to be positive when >5% of keratinocytes were stained. All normal control samples were negative. Positive p16 INK4A was detected in OLP, IOLK, and INF. Significant differences in p16 INK4A positivity were found between OLP (64%) and OLK (28%) (χ 2 = 17.7; P < .01), and between I-OLK and NI-OLK (χ 2 = 4.5; P < .05). No significant difference was found between OLP and INF (43%). In conclusion, positive p16 INK4A in OLP patients seems to be related to reactive inflammatory processes rather than to a risk of progression to oral squamous cell carcinoma.