Coccidioidomycosis is a mycosis endemic to certain areas in the Southwest, mostly Arizona and California, Mexico, and parts of Central and South America. Disseminated coccidioidomycosis is much more common in immunocompromised hosts; therefore, it is frequently encountered by pediatric oncologists in endemic areas. Special attention is needed to diagnose, effectively treat the infection, and appropriately adjust chemotherapy treatment plans to minimize immunosuppression. We describe the presentation and course of 6 patients with coccidioidomycosis who were seen by the pediatric hematology-oncology service at the University of Arizona during the last 3 years. Coccidioidomycosis is a relatively common infection encountered by pediatric oncologists in the southwestern states and should be considered in the differential diagnosis of patients living or visiting these areas.