To evaluate galectin-1, -3 and -7 serum levels as diagnostic and/or prognostic markers for head and neck squamous cell carcinomas (HNSCCs). ELISA was employed to test sera from 102 patients with HNSCCs and from 38 healthy control volunteers for galectin-1, -3 and -7 serum levels. Serum galectin levels were assayed by ELISA and the levels of galectin expression in HNSCCs were determined by means of immunohistochemistry. HNSCCs display significant immunohistochemical amounts of galectin-7, but this galectin cannot be detected in the blood of HNSCC patients. Galectin-3 levels differ significantly (p=0.03) in healthy volunteers and HNSCC patients. Using a threshold value of 4.3ng/ml, galectin-3 serum level enabled a significant level of discrimination (p=0.03) to be established between the cancer patients and the healthy volunteers, with 90% level of specificity and 36% level of sensitivity. The discrimination was even better when using a threshold value of 13.5ng/ml for galectin-1 (p=0.001), with 100% level of specificity and 22% level of sensitivity. A subgroup of stage IV HNSCC patients displayed significantly reduced levels of circulating galectin-1 (p=0.003) and galectin-3 (p=0.001) after treatment as opposed to before. Galectin-3 concentrations in sera from the patients with a metastatic disease were significantly (p=0.01) higher than in sera from the patients with localized tumors. The determination of circulating levels of galectin-1 and -3 could be used to monitor the progression of their disease or their response to therapy.