A 23-year-old man was operated for a skin tumor in the right axilla. Histological examination revealed findings consistent with a syringocystadenoma papilliferum. However, most of the papillary structures showed a disorganized proliferation of atypical cells without invasive growth, that is, a syringocystadenocarcinoma papilliferum in situ. Immunohistochemistry disclosed a different staining profile between the basal cells of the papillary structures and those of the columnar and atypical cells which reacted similarly. However, the atypical cells showed a stronger and more extensive expression of S-100 protein and CD56 than the columnar epithelium and a few of them also reacted with CEA. Ki-67 staining highlighted the increased proliferative activity of the atypical cells. The best antibody for depicting the basal cells was p63. In the present case immunohistochemistry was of little help to support the diagnosis of malignant transformation since the differences between the atypical and regular columnar cells were small and of a quantitative character only.