Objective To investigate the clinical characteristics and diagnosis and treatment of fungal pulmonary embolism, and to improve the understanding of this disease. Methods The diagnosis and treatment of two patients with fungal main pulmonary embolism in the First Affiliated Hospital of Guangzhou Medical University were summarized and analyzed. Literatures were retrieved from Wanfang database, China national knowledge internet database and Pubmed database with search terms of “pulmonary embolism AND mucor”, “pulmonary embolism AND aspergillus”, “pulmonary embolism AND fungi”, “pulmonary embolism AND Candida”, “pulmonary embolism AND cryptococcus”. Results Case 1, a 53-year-old female was referred, with cough, high fever, breathlessness for 2 years, chest pain for 1 year. The patient had rheumatoid arthritis and systemic lupus erythematosus history with long term prednisone treatment. Finally, the patient was diagnosed main pulmonary artery embolism (aspergillus) and disseminated aspergillosis. Although treatment with voriconazole, amphotericin B, and caspofungin were given for more than 1 year, the patient died with uncontrolled aspergillus infection. Case 2, a 67-year-old female was referred with cough, chest distress, chest pain for 8 months, breathlessness for 6 months. The patient had a history of chronic viral hepatitis C. Finally the patient was diagnosed as main pulmonary artery embolism and pulmonary valve endocarditis (aspergillus, mucor). The patient underwent pulmonary artery lesion resection and tricuspid valvuloplasty (DeVega method). After surgery, the patient was delivered with amphotericin B and posaconazole for 3 months. During the follow-up period of 1 year, the patient recovered almost totally without relapse signs. A total of 42 cases of fungal pulmonary embolism from 1980 to 2021 were retrieved (including 2 cases in this article), and 6 of these cases were main pulmonary artery embolism. Of all the cases, the median age was 49 years and 22 (54.3%) were males. 20 cases were immunocompromised. The infection pathogens included: Aspergillus (21, 50%), Candida (11, 26.2%), Mucor (7, 16.7%), and Aspergillus combined with Mucor (1, 2.5%), Coccidioides spp (1, 2.5%), and Cryptococcus (1, 2.5%). Fifteen cases were complicated with infection other than cardiopulmonary. Twenty-two cases were treated with surgery combined with antifungal medicine, and 9 cases with antifungal medicine alone. Twenty-two cases were dead and the overall mortality rate was 52.4%. There were statistically significant differences in the effects of fungal species, dissemination of other organs other than the heart and lung, and surgical treatment on the survival rate. The survival rate of different fungal species was significantly different. Dissemination to organs other than the heart and lungs reduces survival, whereas surgical treatment improves survival. Conclusions Fungal pulmonary embolism, a disease with high mortality, rarely involves the main pulmonary artery. The possibility of fungal pulmonary embolism should be considered when the cause of pulmonary thrombosis is unknown and the anticoagulant effect is poor. Although there is no unified treatment at present, early surgical combined with standard antifungal treatment may improve the prognosis of patients.