Clinical and pathological features of 52 infants and children with atypical teratoid/rhabdoid tumor (ATT/RhT) of the central nervous system are defined. This tumor is typically misdiagnosed as a primitive neuroectodermal tumor (PNET) primarily because 70% of ATT/RhTs contain fields indistinguishable from classic PNETs. Separation of these two tumor types is crucial because the prognosis for ATT/RhT is given even when treatment includes surgery with or without radio and/or chemotherapy. These tumors are most common in infants less than 2 years of age. The cases described in this study arose in intracranially in all but one instance, although one-third had already spread throughout the subarachnoid space at presentation. Clinical signs and symptoms and radiological features do not distinguish ATT/RhTs from PNETs. The tumors are composed entirely (13%) or partly (77%) or rhabdoid cells. Seventy percent contains fields of typical PNET alone or in combinations with mesenchymal and/r epithelial elements. The immunohistochemical profile is unique: epithelial membrane antigen, vimentin, and smooth-muscle actin are positive in the majority of tumors and markers for germ-cell tumors are consistently negative. Abnormalities of chromosome 22 distinguish ATT/RhTs from PNETs, which typically display an i(17q) abnormality.