Abstract Lomentospora prolificans is an environmental mold that is increasingly recognized as an opportunistic pathogen, particularly in immunocompromised hosts. Here we present a case of disseminated Lomentospora in a patient with refractory acute myeloid leukemia. In general, disseminated mold infections can be challenging to diagnose. The diagnosis in this case was delayed due to a false positive direct from a blood culture multiplex polymerase chain reaction result for Candida tropicalis due to amplification of nonviable DNA and misidentification of conidia as yeast forms on gram stain. The Lomentospora isolate was resistant to all commercially available antifungal agents, and the patient ultimately succumbed to the infection. This case provides an opportunity to review disseminated Lomentospora infections, the associated diagnostic challenges, and limited treatment options.