Chronic granulomatous disease (CGD) is an inherited form of primary immunodeficiency caused by impaired phagocyte NADPH oxidase activity, resulting in deficient superoxide production and impaired oxidative burst. It affects approximately 1 in 250,000 children and results in recurrent severe granulomatous infections of virtually any organ system, commonly lung, liver, bone, soft tissue, gastrointestinal tract, bladder, and lymph nodes. Although most patients (75%) are male due to X-linked recessive pattern of inheritance, some girls are affected in the autosomal recessive form or rarely due to skewed lyonization of the X-linked gene. CGD patients develop abscesses and granulomas in response to catalase-positive bacterial organisms, such as Staphylococcus aureus, as well as fungal organisms, mycobacteria, and Nocardia. Aspergillus is reported as the cause of granulomatous pneumonia in up to 79% of cases, but a wide variety of unusual environmentally acquired fungal species have been isolated. Despite a florid granulomatous response, the burden of organisms may be quite low, and identification of organisms on special stains requires careful search. Diagnosis of a specific infectious agent is particularly difficult in needle biopsies, in which only necrosis or acute inflammation may be sampled.