Fungal infections constitute an important cause of morbidity and mortality in HIV-infected patients. The authors describe the case of a 40-year-old healthy male patient with a 2-month history of fever, shivers, asthenia and anorexia, who had lost weight during the past 6 months. Laboratory investigations revealed a positive HIV screening. Computed tomography scans of the chest and abdomen showed thoracic and lumbo-aortic adenopathies. Cryptococcus neoformans was isolated from cultures of blood, bone marrow, cerebrospinal fluid and from material obtained by transbronchial biopsy. Moreover, Cryptococcus spp. were seen in the lymph node biopsy. Pneumocystis jirovecii was isolated from bronchoalveolar lavage, whereas Aspergillus fumigatus and Aspergillus flavus were detected in material from a transbronchial biopsy. The patient initially received treatment with sulfamethoxazole plus trimethoprim and amphotericin B, which resulted in a substantial clinical improvement. After the diagnosis of invasive aspergillosis, amphotericin B was replaced by voriconazole as antifungal therapy and antiretroviral therapy was added. The simultaneous occurrence of three different infectious diseases-disseminated cryptococcosis, invasive pulmonary aspergillosis and Pneumocystis jirovecii pneumonitis-in a HIV-infected patient is extremely rare and there is no doubt that both early diagnosis and treatment are crucial for the patient's chances of survival.