Spitz nevus was first described by Sophie Spitz in 1948 as juvenile melanoma. The lesion is a benign melanocytic tumor, which consists of epiteloid- and spindelshaped cells. Histological is spitz nevus difficult to distinguish from malign melanomas and spitzoid melanomas. Loss of symmetry, loss of maturation in the deep component, nuclear polymorphism and hyper chromatic nucleus are features which can be found in melanomas. Some of these features are often seen in spitz nevus. The purpose of this study was to investigate what help we have from immunohistochemical markers Anti- human HMB-45 (human melanosoma black 45), Anti- human CD99 and Anti- human Ki- 67 antigen to distinguish spitz nevus from spitzoid melanomas and malign melanomas. The study included 21 cases with formalin fixed paraffin embedded tissue. These cases where previous diagnosed as spitz nevus, spitzoid melanomas and malign melanomas. Immunohistochemical staining includes several methods where antibodies are used to detect antigen in tissues. Different visualization systems are used to visualize an antibody- antigen reaction. The most common visualization systems are enzymes. The study was made according to EnVision method (Dako, Denmark), which is an indirect method with secondary antibodies and HRP (horseradish peroxidase) bound to a dextranchain. Paraffin embedded, formalin fixed tissue requires an antigen retrieval before immunohistochemical staining. HIER (heat induced epitope retrieval) is most common use in this purpose. The results were assessed microscopic, where browning endproduct was seen after immunohistochemical staining.  Immunohistochemical staining gave clear positive controls. Anti- human HMB- 45 was present in all immature melanocytic cells. Strong, diffuse staining in superficial component was seen in all cases with Anti- human HMB- 45. Anti- human Ki- 67 was an unpredictable antibody, because lymphocytes had high proliferation and where hard to distinguish from melanocytes. Anti- human CD99 gave a brown stained plasma membrane. There was no difference in staining between spitz nevus and spitzoid melanoma/ malign melanoma with Anti- human CD99. This pilot study shows that staining with immunohistochemical markers is not a helpful tool to distinguish spitz nevus from spitzoid melanomas and malign melanomas.