Talaromyces marneffei (T. marneffei) infection in healthy subjects is rare. A case of osteolysis plus Sweet’s syndrome like lesions associated with T. marneffei infection was presented. The patient was human immunodeficiency virus (HIV) negative. The osteolysis caused by T. marneffei was detected first and Sweet’s syndrome like lesions were developed during antifungal treatment with amphotericin B and itraconazole. After the treatment with amphotericin B, itraconazole and glucocorticoids, the patient’s condition gradually improved.