Primary intracranial lymphoma is uncommon in any age group, but it is especially rare in childhood. This report describes a previously healthy, 14-month-old female infant who developed a primary intracranial immunoblastic (probable B-cell) lymphoma which remained confined to the central nervous system until the time of death, 23 months after diagnosis. She appears to be the youngest patient with documentation of such a diagnosis by light and electron microscopy and by histochemical and immunoperoxidase studies. An immunological investigation was negative. Significant maternal and paternal family histories of malignancy suggest that a genetic predisposition, combined with postzygotic events such as viral infection, may be responsible for this familial cluster of tumors, and for this patient's unusual presentation.