Disseminated ankle mycosis is a life-threatening systemic infection caused by the emerging opportunistic and lethal fungal pathogen Talaromyces marneffei which is more common in HIV-positive patients. However, an increasing number of infections are occurring in HIV-negative patients. Here, we report a case of Talaromyces marneffei infection in HIV-negative patient. A 50s HIV-negative male patient with fever, cough, bloody sputum expectoration, pulmonary sarcoidosis and body rashes was hospitalized at Zhejiang Provincial People's Hospital. CT scanning showed pulmonary multiple nodules with apical bronchial occlusion, patchy infiltration and pathological biopsy demonstrated bronchiolitis obliterans with organized pneumonia and chronic active inflammation of lung tissue with infiltration of numerous lymphocytes, plasma cells, phagocytes and neutrophils. Laboratory tests revealed significantly increased white blood cells count 18.3 ×109/L, neutrophil count 15.34 ×109/L, monocyte count 0.66 ×109/L, platelet count 517 ×109/L, C-reactive protein 116 mg/L, erythrocyte sedimentation rate 112mm/h. The β-D-glucan test was negative (33.06 pg/mL) while fungal culture of broncho alveolar lavage fluid revealed colonies with temperature-dependent dimorphic growth character and Talaromyces marneffei was confirmed by ITS sequencing of the colonies. The patient exhibited radiological improvement and clinical recuperation after intravenously guttae of voriconazole. Talaromycosis in immunocompetent and HIV-negative individuals is relatively rare and is characterized by an insidious onset, various clinical manifestations, and is clinically challenging. Fungal culture and ITS sequencing are warranted for diagnosis Talaromyces marneffei infection. This is the first report on identification of Talaromyces marneffei infection in an HIV-negative patient with skin involvement by ITS sequencing in Zhejiang.