Malic enzymes (MEs) are involved in fatty acid biosynthesis and lipid accumulation, and their expression in sebocytes and sebaceous lesions has not been investigated. The aims of this study were to examine ME1 and ME2 expression in normal skin and sebaceous lesions. A total of 68 cases including 5 specimens of normal skin, 12 facial lesions showing sebaceous hyperplasia, 18 sebaceous adenomas, 10 sebaceomas, 13 steatocystomas, and 10 sebaceous carcinomas were examined for the expression of ME1 and ME2. All benign and malignant sebaceous lesions showed ME1 in clear cells and ME2 in nonclear cells, respectively. ME1/ME2 phenotype is seen in basal sebocytes, basal keratinocytes, sweat glands, and outer root sheath cells and hence not specific. This study demonstrates that ME1/ME2 expression phenotype may have a potential to be a valuable marker for sebaceous differentiation. It is necessary to perform large-scale studies including skin tumors with a clear cell morphology that may mimic sebaceous differentiation.