Background Talaromyces marneffei (TM) primarily infects patients with co-morbidities that cause immunodeficiency, but non-secretory myeloma (NSMM) is rare. TSM and NSMM are associated with fever, osteolysis, and swollen lymph nodes, thereby making it difficult for clinicians to make differential diagnosis. In this case, we describe TM infection coexisting with NSMM. Case presentation We retrospectively reviewed the case of a male (without human immunodeficiency virus infection) with fever, thoracalgia, swollen lymph nodes, and subcutaneous nodules who presented to the First Affiliated Hospital of Guangxi Medical University in February 2014. Chest computed tomography revealed patchy infiltration and positron emission tomography/computed tomography showed increased metabolic activity in the lower-right lung, lymph nodes, left ninth rib, and right ilium. Pathological examination of the lung, lymph nodes, subcutaneous nodules, and bone marrow showed no malignancy, he was diagnosed with community-acquired pneumonia. His clinical symptoms did not improve after anti-bacterial, anti-Mycobacterium tuberculosis, and anti-non-M. tuberculosis treatment. Later, etiological culture and pathological examination of the subcutaneous nodule proved TM infection, and the patient was re-diagnosed with disseminated TSM, which involved the lungs, lymph nodes, skin, bone, and subcutaneous tissue. After antifungal treatment, the patient showed significant improvement, except for the pain in his bones. Imaging showed aggravated osteolysis, and bone marrow biopsy and immunohistochemistry indicated NSMM. Thus, we conclusively diagnosed the case as NSMM with TSM (involving the lungs, lymph nodes, skin, and subcutaneous tissue). His condition improved after chemotherapy, and he was symptom-free for 7 years. Conclusion TM infection is rare in individual with NSMM. Since they have clinical manifestation in common, easily causing misdiagnosis and missed diagnosis, multiple pathological examinations and tissue cultures are essential to provide a differential diagnosis.