Background：Differential diagnosis of keratoacanthoma(KA) from squamous cell carcinoma(SCC) is often difficult, especially when SCC has KA-like features(KA-like SCC). A number of recent studies have been attempted to separate these two entities with the use of immunohistochemical stains. But the results were inconsistent and the studies with KA-like SCC are rarely reported. Objectives：The purpose of this study was to examine the expression patterns of p53 protein and Ki-67 antigen on KA and KA-like SCC using immunohistochemical staining method and to evaluate the usefulness of this method in distinguishing each other. Methods：We performed immunoperoxidase staining(LSAB technique) using monoclonal antibody to p53 protein(PAb1801) and Ki-67 antigen(MIB1) on the formalin-fixed, paraffin-embedded biopsy specimens obtained from 12 patients with KA, 8 patient with KA-like SCC, and 10 patients with well-differentiated SCC. Results：The results were as follows; 1) There was a significant difference in the p53 expression between KA(25%) and SCC group (KA-like SCC=88%, SCC=100%). 2) Mean Ki-67 labeling index was slightly higher for SCC group(KA-like SCC=30.72%, SCC= 31.23%) than for KA(25.30%), but this difference was not statistically significant. 3) In Ki-67 expression, KA showed more pheriperal basal pattern(91%), whereas SCC group showed more diffuse pattern(77%). Conclusion：Our results suggest that KA and SCC are distinct entities of different nature and that these immunohistochemical staining methods can be useful methods in differentiating KA-like SCC from KA.