Invasive fungal infections in children with acute lymphoblastic leukemia have been a major cause of mortality. Recent reports have described increasing incidence of invasive non-Aspergillus mold infections in patients with hematological malignancies. It is always challenging to treat invasive fungal infection and underlying hematological malignancies successfully. Here we report a girl with high-risk acute lymphoblastic leukemia who developed disseminated Cunninghamella bertholletiae infection during induction chemotherapy. This case illustrates the difficulties of diagnosis and treatment of invasive C. bertholletiae infection. It also highlights the necessity for physicians to keep high suspicion and awareness for this infrequent fungal infection.