Abstract: Objective To improve the knowledge of disseminated Penicilliosis marneffei as to help differential diagnosis this disease from tuberculosis in immunocompetent patient. Methods The clinical, chest imaging, bacteriological and pathological characteristics and the diagnostic and therapeutic course from one patient with immunocompetent patient who was admitted to Guangzhou Chest Hospital in November 2007, misdiagnosed initially as tuberculosis and then confirmed as Penicilliosis marneffei, were analyzed retrospectively. Meanwhile the literatures on Pecicilliosis marneffei were reviewed. Results A 60-year-old cantonese male without HIV infection was presented as cough, fever, weight loss, enlargement of multiple lymph nodes, multiple subcutaneous abscesses and rapidly progressive respiratory failure. Chest imaging showed bilateral pulmonary infiltrates, enlargement of mediastinal lymph nodes, bilateral pleural effusion and pericardial effusion. The laboratory examination showed white cell counts increased rapidly up to 45.23×10⁹/L in the peripheral blood,353 cells/μl in CD4⁺ T-lymphocyte count, 1.19 in CD4/CD8 ratio and HIV seronegative. The early culture from the pleural effusion was negative. The patient, who was early diagnosed as TB by pathology twice and failed to response to antituberculosis therapy, was finally proved as a disseminated Penicilliosis marneffei by the fungus positive in clinical specimens from blood, pleural effusion and purulent exudates by microscopy and culture. And the lymph node biopsy was performed again to prove the disease, with microscopic demonstration of intracellular Penicillium marneffei yeast cells in the infected tissue. The antituberculosis therapy and corticosteroid treatment were discontinued, and the antifungal therapy with voriconazole was implemented. The patient developed subsequently respiratory and circulatory failure, and died after 4 days with voriconazole administration. Conclusion Patients with Penicilliosis marneffei have a poor prognosis without the appropriate antifungal treatment.The early clinical features, imaging findings and pathological characteristics of the disease were easily confused with those of TB. Patient from areas where the infection is endemic, Penicillium marneffei infection should be suspected when the patient failed to response to antituberculosis therapy even if immunocompetence. Early identified the fungus in clinical specimens from purulent exudates by culture at different temperatures (25 ℃ and 37 ℃) should be considered.