BACKGROUND Circulating tumor markers are valuable adjuncts in the management of several malignant lesions, including germ cell tumors and adenocarcinomas of the breast, colon, prostate, and ovary. However (to the authors' knowledge), currently, no serologic markers have been shown to have prognostic value for patients with squamous cell carcinomas of the head and neck (SCCHN). METHODS Novel and existing markers were evaluated prospectively in patients with SCCHN: The levels of lipid-associated sialic acids (LASA), squamous cell carcinoma circulating antigen (SCC-Ag), carcinoembryonic antigen (CEA), and lactic dehydrogenase (LDH) were evaluated in 52 patients: 42 with active measurable SCCHN and 10 with no clinical evidence of active disease after treatment (NED). RESULTS In patients with active disease, LASA, SCC-Ag, CEA, and LDH were elevated in 71%, 33%, 27%, and 18%, respectively, and in seven patients with distant metastasis (M1) in 100%, 86%, 57%, and 33%, respectively. None of the markers were elevated in the NED group. The incidence and magnitude of LASA and SCC-Ag elevations correlated with the extent of disease (active disease versus NED, Stage III versus IV, T0-3 versus T4 primary lesions, M0 versus M1). LDH and CEA elevations correlated primarily with the presence of distant metastases. CONCLUSIONS LASA appears to be a promising sensitive marker of SCCHN, followed in decreasing order of sensitivity by SCC-Ag, CEA, and LDH. Additional study to evaluate the specificity of LASA and its correlation with tumor response to therapy is warranted.