Background: Malignant pericardial effusion with cardiac buffer secondary to endometrial cancer is exceptional and can be fatal for these patients if it is not recognized in time; however, due to the rarity of this type of case, there is no standardized treatment. Case: We present the case of a patient who went to emergency room due to dyspnea of small exertion that worsened; upon arrival, data of pulmonary thromboembolism were corroborated, and in secondary studies, data of cardiac tamponade were observed, and pericardial window was performed as initial treatment draining 750 mL of pericardial fluid. Later, a cytopathological study of the pericardial fluid revealed adenocarcinoma cells, continuing its diagnostic approach, and found that the primary tumor was adenocarcinoma of the endometrium. Conclusion: Cardiac tamponade is a rare and fatal complication, which makes it a complex pathology for diagnosis and treatment. Therefore, it is important to publicize this type of case to improve current management.