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A 74-year-old man presented with gradual wall thickening of a cystic lung lesion. Serologic tests indicated Aspergillus infection, but neither fungal organisms nor evidence of malignant disease were recovered from repeated sputum collections, a bronchoscopic lung biopsy specimen, or bronchial washings. Treatment with antifungal agents did not result in clinical improvement. Surgical resection of the lesion demonstrated both squamous cell carcinoma and aspergillosis. These distinct disorders share common radiologic manifestations that can present a diagnostic challenge, as in the present case.