β-HCG belongs to the glycoprotein hormone family and is usually assess to exclude pregnancy for patients potentially eligible to chemotherapy, especially during clinical trials. We studied non-small-cell lung cancer (NSCLC) patients that were found with elevated serum β-HCG level during clinical trial screening. The first case is a 45-year-old woman who presented with a stage IV undifferentiated carcinoma of the lung eligible for chemotherapy. When screening the patient for a clinical trial combining platinum-based chemotherapy and targeted therapy, the plasma β-HCG level was 19 IU/L (0-5 IU/L). The second case is a 64-year-old woman presented with stage IV poorly differentiated adenocarcinoma of the lung. When screening the patient for the same clinical trial combining platinum-based chemotherapy and targeted therapy, the plasma β-HCG level was β-HCG 13 IU/L (0-5 IU/L). The serum dosages were double-checked and confirmed elevated β-HCG level. The gynecological work-up definitely rules out an improbable pregnancy. The pathological examination was also checked and confirmed in the two cases a primary lung cancer. An immuno-histochemical reassessment of the pathological specimens with additional tests was performed: for one patient 25% of tumor cells expressed β-HCG. As pregnancies were ruled out, the two cases were extensively discussed with the promoter and the patients finally treated within this clinical trial. The treatments are ongoing. β-HCG is a specific marker for trophoblastic tumors of placenta and gestational tumors. Ectopic expression of β-HCG was found in 20-40% of all common epithelial carcinoma, especially for tumors of the stomach, ovary, liver and lung. Only few cases have been reported in the literature. However, in a young patient with high serum levels of β-HCG two questions arise: is there a place for pregnancy? Are the pathology results accurate? All this could delay the appropriate management of these patients and also potentially prevents the participation of innovative therapeutic strategies. Therefore, knowing this rare but possible expression of β-HCG by lung tumors may speed out the gynecological work-up and the reevaluation of the histological samples in order to minimize the delay in the care of these patients and give them a chance to have new innovative drugs within clinical trial.