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Recently, Talaromyces marneffei (T. marneffei) has been reported in human immunodeficiency virus (HIV)-negative patient with underlying diseases, such as oral cancer, colon cancer, haematological malignancies, connective tissue disease, diabetes mellitus, and corticosteroids or immunosuppressive agents. Similar to HIV-positive ones, such patients were observed with CD4 lymphocytopenia.We reported a case of a 45-year-old woman who was diagnosed with disseminated T. marneffei and Mycobacteria kansasii (M. kansasii) with papillary thyroid cancer as the underlying disease. T-cell subsets counts, CD4 T-cell%, CD8 T-cell%, CD4/CD8 ratio, and NK cell% were all turned out to be normal.Based on bronchoalveolar lavage fluid and skin lesions secretion cultures, blood culture, the patient was diagnosed with disseminated T. marneffei and M. kansasii. Pathological examination reported papillary thyroid cancer with cervical lymph node metastasis.The patient received the combined and longer antifungal therapy and drug regimens for M. kansasii. She had total thyroidectomy with radical neck dissection to treat the papillary thyroid cancer.The patient had a favorable outcome for 19 months without recurrence.T. marneffei could infect non-HIV individuals with underlying disease under the condition of normal T-cell counts. The symptoms were lack of specificity and were more likely to be misdiagnosed. Such patients with unidentified T-cell dysfunction or other unidentified primary immunodeficiency disorders may prone to coinfect with other opportunistic pathogens, such as M. kansasii. Compared with HIV-positive ones, they need combined and much longer antifungal therapy.