Mycotic immunodiagnosis was performed in 325 patients with clinical evidence of systemic mycoses, over a 5-year period, from different hospitals of Mexico City. Results showed 168 individuals that presented one positive serological test to Histoplasma capsulatum antigens. From these, only 27 patients were serologically positive to two or more tests, such as tube precipitin, immunodiffusion, complement fixation, and ELISA, and developed signs and symptoms of a histoplasmosis clinically classified as primary pulmonary. Four of them presented an underlying disease including one positive HIV patient. Twenty-two came from endemic histoplasmosis zones of the country and most of them acquired the disease in caves or uninhabited houses. The diagnosis of histoplasmosis should be based on reliable laboratory data which could raise more significant information of its incidence in Mexico.