Penicillium marneffei is a rare fungal pathogen which can cause human infections in people predominantly living in South-east Asia and the southern portion of China. We report three cases of systemic P. marneffei infection in patients infected with HIV who lived in or had travelled to endemic areas. The clinical manifestation includes high fever, chills, weight loss, general malaise, chronic cough, haemoptysis, multiple skin lesions, abnormal liver function, etc. Chest X-ray showed single or multiple cavitary lesions with smooth or irregular thin wall. P. marneffei is cultured from blood, sputum, skin biopsy, sono-guide aspiration and bronchoscopic biopsy. After antifungal therapy with intravenous amphotericin B or oral fluconazole, skin lesions resolved completely within 2 weeks and cavitary lesions in the lungs changed to chronic fibrotic and interstitial processes after several months to a few years later. Our two cases had been treated as either pulmonary tuberculosis or suspected malignancy. A definite diagnosis and early treatment are important because this fungal infection is a marker of AIDS in South-east Asia.