Endometrial cancer is the most common cancer of the female genital tract. It can rarely metastasize to the pleura and present as a malignant pleural effusion. Here we present the case of a 61-year-old female with two primary malignancies, breast and endometrium, who presented to us with shortness of breath. Imaging was suggestive of a malignant pleural effusion. Diagnostic and therapeutic thoracentesis were performed that were initially suggestive of a breast source. However, final pleural fluid studies showed endometrial serous carcinoma as the source of the effusion. The patient received pembrolizumab and lenvatinib treatment and continues to be followed up in our clinic.