Recently, tumor markers have been used in diagnosis and assessment of treatment outcome. However, low concentrations of tumor markers are detected in patients with nonmalignant diseases and in healthy subjects. The purpose of this study was to clarify the clinical usefulness of urinary 6-HMP concentrations in the diagnosis of oral cancer. The 6-HMP concentration was measured in patients with oral cancer and those with nonmalignant diseases. In patients with nonmalignant disease, the presence of acute inflammatory diseases correlated with markers of infection. In addition, the usefulness of a combination assay with urinary L-fucose for the diagnosis of oral cancer was evaluated. The results are summarized as follows. 1. Increasing urine volume to 50μ 1 enhanced the sensitivity of the method, and the normal range of urinary 6-HMP concentration was less than 0.079μg/ml in 89 healthy subjects. 2. The sensitivity, specificity, and accuracy of the method in patients with oral cancer were 69.8%, 60.5%, and 63.3%, respectively. 3. In patients with systemic infections, the concentration of 6-HMP correlated with WBC, ESR, and CRP (r<0.01), but it did not correlate with these markers of inflammation in patients with head and neck infection. 4. The positive rates of urinary 6-HMP and urinary L-fucose were 77.1% and 51.1%, respectively, in the combination assay, with urinary L-fucose in 35 patients with oral cancer. With the cornbination assay, the positive rate was enhanced to 82.9%. These results suggest that the measurement of urinary 6-HMP levels provides a useful tumor marker in the diagnosis of oral cancer.