Background: Cryptococcal pneumonia is an uncommon lesion in immune-competent adults. Histological evidence of Cryptococcus neoformans is a gold criterion for diagnosis. Here we report a case firstly misdiagnosed as tuberculosis from a lung biopsy. Methods: Chest computed tomography (CT) scan and CT-guided puncture were performed for diagnosis and blood tests explored for the latent etiology. Results: Chest CT scan images showed multiple nodules in the left peripheral lower lobe. Histopathology demonstrated multiple granulomatous inflammatory response lacking evidence of Cryptococcus neoformans, acid-fast staining was negative, serum cryptococcal antigen was positive. Conclusions: Serum cryptococcal antigen has high specificity in cryptococcal pneumonia.