The correlation between proteinase activities and invasive and metastatic potentials was investigated by comparing three different kinds of tumors. Extracts from tumor homogenate of 11 squamous cell carcinoma (SCC), 5 basal cell epithelioma (BCE), and 8 seborrheic keratosis (SK) were prepared in order to examine the activity of acid phosphatase and proteinases such as cathepsin B and D, type I and IV collagenase, and plasminogen activator (PA). There was no difference observed between acid phosphatase and cathepsin D activities among the three tumors. Cathepsin B and PA activities were slightly elevated in SCC. Type I collagenase activity of SCC was 9-fold higher than that of SK (p less than 0.01), and type IV collagenase was 3-fold higher per tissue DNA (p less than 0.05). Type I and IV collagenase of BCE were elevated per tissue protein but not elevated per tissue DNA. Correlation was found between the level of cell differentiation in SCC and the activities of cathepsin B, PA, and type I collagenase. Poorly differentiated SCC exhibited a tendency to have higher proteinase activities. Proteinases that showed high activities in malignant tumor homogenate may be related to the degradation of the surrounding cell matrix in addition to intracellular metabolism. Type I and IV collagenase, in cooperation with cathepsin B and PA, might play a major role in invading the dermal stroma and basement membrane.