YKL-40, a 40 kDa plasma protein, is secreted by macrophages, neutrophils, chondrocytes, vascular smooth muscle cells and cancer cells. High plasma YKL-40 is found in patients with inflammatory diseases and cancer, but it is not known how the protein is expressed in tissues. This immunohistochemical study was carried out with the purpose of mapping and grading cytoplasmic expression of YKL-40 in normal human tissue. Bovine serum albumin had to be used for pre-incubation in order to eliminate background staining of YKL-40. The majority of cells were stained, but the intensity varied, not just among different cell types but also within the same cell type. Cells known for exerting a high metabolic activity, i.e., high producing cells or cells with high turn-over, tended to show the most intense cytoplasmic staining, which was weak or lacking in cells with no or little activity. Many of these positive cells probably contribute to the YKL-40 found in plasma in healthy subjects in accordance with previous findings on their in vitro production of the protein. In conclusion, all cells with a functioning nucleus appeared to be capable of expressing YKL-40 in their cytoplasm, the intensity of which was dependent on cellular activity.