Hematopoietic stem cell transplantation (HSCT) can be lifesaving for some of the deadliest hematologic diseases. However, immunosuppression, polypharmacy and risk of infectious complications associated with HSCT can increase morbidity and mortality for recipients. Incidence of acute kidney injury (AKI) after HSCT can be as high as 70%, and concomitant infection can be a therapeutic challenge for oncologists, nephrologists and infectious disease specialists. We illustrate this challenge in the case of a 31-year-old man with acute lymphoblastic leukemia who underwent a double cord HSCT complicated by GvHD, systemic cryptococcal and BK virus infections and AKI. Kidney biopsy showed round to cup-shaped organisms with occasional budding, consistent with Cryptococcus and thrombotic microangiopathy. We discuss our findings and a literature review of disseminated cryptococcal infection with renal involvement after HSCT.