Background: The objective of this study was to assess the potential clinical value of the concentration of soluble salivary E-cadherin (sE-cadherin) compared with the clinical value of the presence of membranous E-cadherin (mE-cadherin) in oral squamous cell carcinoma tumor tissues. Material and Methods: Data regarding patient demographics, clinical stage, saliva and tumor tissue samples were collected. The saliva was analyzed for sE-cadherin protein levels and was compared to the mE-cadherin immunohistochemical expression levels in tumor tissues, which were assessed via the HercepTest® method. Patients without cancer were included in the study as a control group for comparisons of the sE-cadherin levels. Results: sE-cadherin levels in the saliva of patients without cancer were lower than those in patients with cancer, and the difference was statistically significant (p=0.031). Low mE-cadherin expression was statistically significantly associated with lymph node positivity (p=0.015) and advanced clinical stage (p=0.001). The inverse relationship between mE-cadherin and sE-cadherin was significant in terms of lymph node positivity (p=0.014) and advanced clinical stage (p=0.037). Conclusions: The results suggest that sE-cadherin levels are significantly increased in patients with oral cancer and that its low expression within the membrane as well as the progression of the disease appear to be inversely associated with levels of sE-cadherin in the saliva.