Choriocarcinoma (CC) tends to metastasize early into various organs and may exhibit peculiar clinical behaviors specific to metastases. Although chemotherapy has revolutionized the survival of most patients, the mortality rate remains high in cases at ultra high-risk, which may be associated with multiple organs involvement and intolerable toxicity resulting from combination chemotherapy. Here, we illustrate a 46-year-old woman patient with oral and lung lesions whose clinical and morphological heterogeneity misled the preliminary diagnosis. According to the initial pathological report of oral squamous cell carcinomas with lung metastasis and a combined positive score = 100, she received first-line immunotherapy plus two-drug chemotherapy, which obtained a surprisingly favourable outcome. Then, CC was identified by a high level of beta human chorionic gonadotropin (β-HCG) in serum and biopsies. DNA polymorphic analysis revealed its gestational origin, and a more aggressive standard regimen was subsequently implemented. However, the patient suffered repeated vomiting and myelosuppression, and the duration of treatment was significantly prolonged. Ultimately, she succumbed to death. The clinical course of this report helps to improve the understanding of this disease. We consider immune checkpoint inhibitors as potential first-line alternatives for ultra-high-risk CC patients, which provide a therapeutic reference for clinicians.