Cathepsin D is a lysosomal aspartyl endopeptidase which degrade the extracellular matrix and proteoglycan. It is well known that tumor metastasis is a major prognostic factor in the survival & prognosis of the patient with head and neck cancer. This study was designed to investigate the relationship between cathepsin D expression and lymph node metastasis in head and neck squamous cell carcinoma, using immunohistochemical methods. Tissue were obtained from 50 patients with head and neck squamous cell carcinoma who underwent the surgery of primary tumor resection and radical neck dissection. The reults were as follows. 1) The positive reaction of cathepsin D was identified as characteristic granules both in carcinoma cells and extracellular matrix. The strong positive cathepsin D expression(2+ or 3+), as defined by cytoplamic immunoreactivity greater than 30% of the cancer cells, was found in 31 cases(62.0%). 2) Lymph node metastasis of patient wuth strong positive cathepsin D expression was 83.9%(26/31) compared with closely related with the lymph node metastasis(p=0.006). 3) Strong positive cathepsin D expression was noted in larger tumor size, increased number of metastatic lymph nodes and poorly differentiated histologic type(p<0.05). 4) Cathepsin D expression of the metastatic lymph nodes was stronger than that of the corresponding primary tumors(p=0.009). 5) There was no significant correlation between the patient age, clinical stage(TNM classification) and immunohistochemical detection of cathepsin D expression in head and neck squamous cell carcinoma. These results suggest that cathepsin D may be a biochemical parameter to predict the metastatic potential and aggressiveness of head and neck squamous cell carcinoma.