The histopathology of papillary tumours of the pineal region (PTPR) closely resembles that of ependymomas and choroid plexus tumours. Therefore, immunohistochemical staining profiles were investigated in a series of 15 PTPR. In addition to cytokeratin, synaptophysin and glial fibrillary acidic protein expression, PTPR were examined for the presence of dot- or ring-like epithelial membrane antigen (EMA) immunoreactivity typically encountered in ependymoma, staining for inwardly rectifying potassium channel Kir7.1 and stanniocalcin-1 (specifically expressed in choroid plexus tumours) as well as microtubule-associated protein-2 (MAP-2). Furthermore, comparative genomic hybridization was performed in five PTPR. Cytokeratin was expressed in all PTPR examined, whereas glial fibrillary acidic protein and synaptophysin staining were absent. Dot- or ring-like EMA immunoreactivity was only observed in 1 out of 15 PTPR. Membranous Kir7.1 and cytoplasmic stanniocalcin-1 staining were present in the minority of PTPR (3/15 and 4/15, respectively). In contrast, MAP-2 immunoreactivity was encountered in 13 out of 15 PTPR, but was significantly less frequently observed in a series of choroid plexus tumours (7/37). PTPR mainly presented with chromosomal losses affecting chromosomes 10 (4/5 cases) and 22q (3/5 cases) as well as gains on chromosomes 4 (4/5 cases), 8 (3/5 cases), 9 (3/5 cases) and 12 (3/5 cases). To conclude, the majority of PTPR can be distinguished from ependymomas and choroid plexus tumours by absent staining for epithelial membrane antigen, Kir7.1 and staniocalcin-1 as well as the presence of distinct MAP-2 immunoreactivity. Antibodies directed against these antigens are thus expected to be valuable markers in the diagnosis of papillary tumours located in the vicinity of the third ventricle.