A great number of lichenoid lesions have overlapping clinicopathological features, so the use of adjunct tests to establish definitive diagnosis is recommended for correct management and prognosis of the lesions. In this context, direct immunofluorescence (DIF) can be a useful tool. Thus, this study aimed to characterize the clinical, histopathological, and DIF pattern in patients with oral lichen planus (OLP) and patients with oral lichenoid lesions (OLLs). Patients with OLP and patients with OLL were characterized and compared with patients with mucous membrane pemphigoid, pemphigus vulgaris, and fibrous hyperplasia through a cross-sectional study. Patients with OLP (n = 30) and patients with OLL (n = 26) were mostly white women in the fifth decade of age, with reticular lesions mainly on the buccal mucosa. All patients with OLP and half of the patients with OLL showed liquefaction degeneration at the basal cell layer and a band-like lymphocytic infiltrate in the subepithelial tissue. Twenty-two patients with OLP (73.3%), 10 with OLL (38.4%), 25 with mucous membrane pemphigoid (96.1%), and all with pemphigus vulgaris (100%) had positive DIF. There was no positive DIF in patients with fibrous hyperplasia. The most frequent DIF pattern in patients with OLP and patients with OLL was linear fibrinogen at the basement membrane zone, and a logistic regression model for positive DIF found statistically significant difference in OLP versus OLL (odds ratio, 3.73; confidence interval, 1.23–11.38). Although clinical and histopathological features are sufficient for diagnosing most of the patients with OLP and OLL, DIF is a key tool in differentiating some lichenoid lesions and could improve the diagnosis of OLP and OLL, especially in lesions showing typical clinical and histological features of OLP.