A case of chronic sinus disease due to morphologically atypical Aspergillus flavus is described. Multiple fungal isolates sporulated poorly or not at all, displaying unusual color and microscopic morphology, including the absence of typical vesicles and phialides, which caused the isolates to resemble several other fungal genera superficially. The patient received multiple antifungal therapies over at least 10 years with various azole drugs, including voriconazole, itraconazole, and posaconazole. We speculate that this lengthy exposure to azole antifungal drugs may have caused or promoted the atypical morphology seen in these isolates.