The purpose of this study was to assess the safety and reliability of ultrasound-guided fine needle aspiration biopsy (US-guided FNAB) combined with modified Papanicolaou's staining in the diagnosis of pulmonary cryptococcosis. The study included 10 patients (9 men, 1 woman, 28-70 yr). Percutaneous US-guided FNAB was performed through a puncture probe with central channel guidance (n = 8) or in a 'free-hand' manner (2), depending on the size of the lesion and the experience of the operator. Sonography disclosed homogeneously hypoechoic lesions with air bronchograms over the peripheral or central portion in nine patients, and occasional heterogeneous echogenicity with necrotic tissue without air bronchogram in one. Thirteen lesions were found on the chest radiographs of the 10 patients; these could be divided into three patterns: infiltrates (2), nodules or masses (7), and consolidation (4). Using US-guided FNAB and immediate modified Papanicolaou's stain, a diagnosis of pulmonary cryptococcosis was confirmed in nine of the 10 patients. The remaining case was proven by surgical resection. No major complications developed after US-guided FNAB. We conclude that this technique, combined with modified Papanicolaou's staining, provides a safe, rapid, and reliable method for diagnosing pulmonary cryptococcosis.