The incidence of malignant tumors in the primary immunodeficiency diseases is dramatically increased. Four patients with primary immunodeficiencies who developed fatal malignancies are reported. Lymphoreticular tumors and leukemia predominate in most conditions, but epithelial neoplasms are the most common tumors in selective IgA deficiency, and they comprise over one fourth of malignancies in common variable immunodeficiency. With the exception of common variable immunodeficiency and the Wiskott Aldrich syndrome, hyperplasia of lymphoid tissue usually does not occur. Lymph node enlargement in any of the other immunodeficiencies is therefore most likely secondary to malignancy. Benign gastrointestinal nodular lymphoid hyperplasia occurs frequently in common variable immunodeficiency and in some instances may be impossible to differentiate roentgenologically from lymphoma.