The regeneration of the oral mucosa is zinc- and vitamin A-pathway dependent. Hyperkeratoses, a disturbed immune system and a higher incidence of oral malignancies have been reported in cases of deficiency. In this study, blood samples were taken from 97 patients with oral lichen planus, oral leukoplakia, oral squamous cell carcinoma (OSCC), and a control group. Besides routine blood analysis, serum levels of zinc (Zn), vitamin A (Vit A) and retinol binding protein (RBP) were identified. Mean values in lichen ruber planus were Zn 784 micrograms/l, RBP 5.26 mg/dl and Vit A 656 ng/ml; in leukoplakia Zn 696 micrograms/l, RBP 5.30 mg/dl and Vit A 652 ng/ml; and in OSCC Zn 659 micrograms/l, RBP 5.00 mg/dl and Vit A 617 ng/ml. Patients with lichen ruber planus showed no statistically significant differences, whereas in leukoplakia patients there were statistically lower values for Zn compared to the control group and the lichen ruber planus group (P < 0.05). Patients with oral malignancies showed lower serum levels for Zn, RBP and Vit A. Compared with the control group and the lichen ruber planus group, differences of the serum Zn levels proved to be statistically significant (P < 0.01). In patients with oral leukoplakia and patients with oral carcinoma and Zn deficiency, a substitutional therapy should be considered.