Background Hyaluronan (HA) is most likely associated with tumor invasion and metastasis. Studies have shown that HA levels are often increased in serum of patients with various malignant tumors. The purpose of this study was to determine the levels of serum hyaluronan in patients with oral cancer and evaluate the value of serum HA in adjuvant diagnosis, staging and monitoring treatment response in these patients. Methods Eighty-four hospitalized patients with oral cancer, 65 patients with benign tumors in the oral and maxillofacial region and 67 healthy individuals were included in this investigation. Venous blood was collected from these patients and the healthy individuals before therapy. One week after therapy, venous blood was collected once again in 43 patients with oral cancer. Serum samples were obtained and serum HA levels examined. Results The serum HA concentration was significantly higher in oral cancer patients than inpatients with benign tumors and in healthy controls (P 0.05). The serum HA level in patients with stages III and IV disease was higher than in patients with stages I and II disease, but there was no significant difference in the HA level between stages I and II nor between stages III and IV (P>0.05). After a complete treatment the HA levels in patients with oral cancer became lower than before treatment, but the difference was not significant (P>0.05). Conclusions The results of this study suggest that the determination of HA levels may provide additional information in diagnosis of oral cancer, but its usefulness as an adjunct in clinical staging and in monitoring treatment response was limited.