OBJECTIVE: To investigate diagnostic histopathology and ultrastructure features of primary pulmonary cryptococcosis (PC). METHODS: Clinical data and pathologic findings of 27 cases of PC were retrospectively reviewed, light and electron microscopic evaluations and histochemistry stain studies were performed. RESULTS: The specimens consisted of 2 fine-needle aspiration lung biopsies and 25 cases of open lung biopsies. Cryptococcosis granuloma formation was identifiable by histopathological examination in 25 of 27 cases, with gum-like lesion and fungi in the remaining 2 cases. The detection rates of cryptococcus neoformans (CN) by mucicarmine (MC), periodic acid-Schiff (PAS), alcian blue (AB) and Grocott methenamine-silver (GMS) were 87.0% (20/23), 100% (27/27), 66.7% (18/27), and 100% (23/23) respectively. Under the electron microscope, most CN had a simple structure with a few organelles. The capsule was seen in all organisms. A percentage of the organisms showed nuclei, nucleoli, mitochondria and vacuoles. The detection rate of CN by EM was 91.7% (11/12). CONCLUSIONS: The clinical manifestation and imaging of PC are nonspecific for PC. Lung biopsy is the major diagnostic modality. The detection rate by electron microscopy was quite high. Therefore, a correct diagnosis of pulmonary cyrptococcosis should rely on the combination of histopathological evaluation, histochemistry staining and/or electron microscopic examination.