Tehran University of Medical Sciences Case Reports in Clinical Practice 2538-2683 10 5 2026 05 04 218 223 EN Arian Karimi Rouzbahani Western Health, Department of Urology, Melbourne, Australia. Yahya Baharvand Irannia Department of Internal Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran. Shahram Ahmadi Somaghian Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran. Golnaz Mahmoudvand USERN Office, Lorestan University of Medical Sciences, Khorramabad, Iran. Omid-Ali Adeli Department of Pathology, Lorestan University of Medical Sciences, Khorramabad, Iran. Reza Yusofvand Department of Internal Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran. 2025 11 16 2025 12 21 The incidence of multiple primary malignancies (MPMs) has risen in clinical practice; however, cases involving three or more primary cancers remain rare. A 56-year-old postmenopausal female with a significant familial cancer history developed four primary malignancies: papillary renal cell carcinoma, endometrial stromal sarcoma, colon adenocarcinoma, and invasive ductal carcinoma of the breast. The patient passed away after one year of receiving palliative treatment for her metastatic breast cancer. This study reviews 33 cases of MPMs, primarily involving breast, colon, and uterine cancers, mostly in women over 60. Genetic predisposition plays a significant role, with 35.5% having hereditary cancer syndromes. This report emphasizes the importance of considering new masses in cancer patients as potential new malignancies. Early detection using fluorodeoxyglucose positron emission tomography (FDG-PET), implementing genetic testing, and timely cancer screenings in high-risk families significantly improve patient outcomes and management. https://crcp.tums.ac.ir/index.php/crcp/article/view/1136 https://crcp.tums.ac.ir/index.php/crcp/article/download/1136/750