Although the prevailing dogma states that keratin filaments are the hallmark of keratinocytes and other epithelial cells, recent publications suggest that they may be expressed by a variety of normal and malignant cells of different embryonic origin. Keratin expression has been reported in fibroblasts and endothelial cells as well as in various sarcomas. Also, some human melanomas express keratins in addition to the traditional diagnostic markers of differentiation, such as S-100 and melanocyte-specific antigens. Many studies have shown that cultured cells obtained from various melanomas express keratin. Most recently, keratin expression has also been shown in cultured melanocytes of normal skin. We now report that normal human melanocytes in vivo express keratin 16 (K 16) but not keratins 1, 5, 8, 10, 14, or even keratin 6, the type 11 partner that is normally expressed with K16 in keratinocytes. Similarly, melanocytes in vitro express K 16 but not K6. Keratin 16 expression in vivo was present in basal melanocytes in specimens derived from donors (0-77 years) and from different anatomic locations, suggesting that keratin 16 is constitutively expressed by all melanocytes. It appears that keratin expression may be more prevalent than previously assumed, and that these cytoskeletal filaments may play important roles in tissues and cells other than epithelia.