The confirmation of Histoplasmosis especially becomes difficult in cases when the patient divulges no details on the history of his exposure to the soil / dust contaminated with H. capsulatum fungus. Physical examination fails to yield any definite result as the early symptoms of this disease are similar to the symptoms of flu. Therefore, a culture test of blood, sputum and sometimes tissue biopsy samples are done. However, these tests can only be done with the aid of a special media that supports the growth of H. capsulatum fungus. 

It is observed that this test confirms the presence of this disease in about 60 per cent of patients reporting the chronic form of the disease. On the other hand, the test concludes a positive result in just about 15 per cent of patients complaining acute Histoplasmosis. Further, there are numerous serology tests that can be done by acquiring blood, urine or cerebral spinal fluid samples.

These tests are known to be more reliable than culture tests as they yield precise results for patients suffering from all the three forms of the disease, symptomatic, chronic, or progressive disseminated Histoplasmosis. In addition, stains of tissue, blood, bone marrow, lymph node aspirates, sputum and other fluids in the body are subjected to microscopic examination to confirm the presence of H. capsulatum fungus.