Serum matrix metalloproteinases (MMPs) and the macrophage colony-stimulating factor (M-CSF) are of potential interest as serum tumor markers in various malignancies. There is still a lack of reliable tumor markers in patients with squamous cell carcinoma of the head and neck (SCCHN). Therefore, the tumor marker potential of MMPs and M-CSF was investigated in these malignancies. Serum of 59 patients suffering from SCCHN and of 59 healthy volunteers was obtained. The concentration of MMP-3, MMP-8, MMP-9, and M-CSF was determined by sandwich enzyme immunoassays. The MMP- 3, -8, -9, as well as the M-CSF serum concentrations were significantly elevated in the patient group, compared to the healthy controls (p<0.001, p<0.05, p<0.001, p=0.002). There was significant correlation between the M-CSF and the MMP-3 serum concentration (p<0.0001), and between the M-CSF and the MMP-8 serum concentration (p=0.005). A significant correlation with the tumor stage was found only for MMP-8. MMP and M-CSF serum concentrations are of potential interest as serum tumor markers in SCCHN.