A case of fungal sinusitis caused by Paecilomyces lilacinus that was unresponsive to amphotericin B and involved a patient with acute myeloid leukemia is described. Histologic examination of sinus tissue and periorbital bone demonstrated invasion by a fungus with septate hyphae, which was identified in culture as P. lilacinus. The isolate was resistant to amphotericin B but susceptible to itraconazole. The patient responded clinically when itraconazole was added to the treatment regimen. Invasive aspergilar infections are frequently diagnosed by histology. Other fungi such as Fusarium, Pseudallescheria, and Paecilomyces species also produce hyphae in tissue and can be confused with Aspergillus species. However, these pathogens may be resistant to amphotericin B. Since alternative therapy is now available for infections with some of the amphotericin B-resistant fungi, such as P. lilacinus, every effort should be made to recover the fungal pathogen so that effective treatment can be administered.