The majority of fungal infections are caused by species such as Candida and Aspergillus. Other rare and emerging opportunistic fungal infections are on the increase. Risk factors for such infections include receipt of antimicrobial agents, chemotherapy, immunosuppression secondary to hematopoietic stem cell or solid organ transplantation, neutropenia, presence of indwelling intravascular catheter, prior hemodialysis, or previous fungal colonization. We present here the first 2 reports of fatal and invasive Chaetomium infections in pediatric patients. The first case occurred in a child with acute myeloid leukemia (AML) and the other in a child with hemophagocytic syndrome (HSP).