Discoid lupus erythematosus lesions show hyperkeratosis and atrophy, which may reflect abnormal epidermal proliferation, differentiation, or both. In this investigation, markers for epidermal proliferation, differentiation and inflammation were studied in cutaneous lesions of discoid lupus erythematosus. Frozen sections of biopsy specimens from 20 patients were examined immunohistochemically regarding Ki-67 staining and keratin 16 expression (parameters for proliferation), and the expression of keratin 10, involucrin, and filaggrin (parameters for differentiation). The inflammatory infiltrate was characterized with the use of antibodies against T lymphocytes, monocytes/macrophages, and Langerhans cells. With these markers, epidermal proliferation was found to be increased in discoid lupus erythematosus. Keratin 10 expression, a marker for early differentiation, showed the pattern of normal skin. Involucrin and filaggrin, markers for terminal differentiation, were expressed already in the lower part of the stratum spinosum, whereas in normal skin these markers were restricted to the stratum granulosum and the upper layers of the stratum spinosum, and the stratum granulosum and stratum corneum, respectively. Infiltrate analysis revealed the well-established picture. We conclude that in cutaneous lesions of discoid lupus erythematosus, hyperproliferation is combined with normal early differentiation and premature terminal differentiation of keratinocytes.