Squamous cell carcinoma antigen (SCCA) has been used as a promising aid for the management of squamous cell carcinoma of various sites. Recently, SCCA gene has been demonstrated at the 18q21.3 locus, and the exon sequence of SCCA gene shows a close homology with inhibitory-type serpins. Actually, SCCA inhibits human chymotrypsin, papain, calpain 1, or cathepsin L. Since serpins are involved in the intercellular adhesion events, it is likely that SCCA takes some part in the malignant behavious of squamous cancer, e.g. invasion or metastasis. SCCA is also present in the spinous and granular compartments of the mature squamous epithelium. Southern blot analysis of the SCCA gene in several vertebrates reveals that it is present in most of the eutherian species, but not in the metatheria, bird, reptile, amphibian or teleost. Thus, SCCA appears to play important roles in the stratification or differentiation of the integument. The present paper describes the expression and function of SCCA, and discusses its possible role in the biological behavious of malignant and nonmalignant squamous cells.