Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 20 3 2026 09 29 268 277 Amirhossein Gholamlou Department of Internal Medicine, Hazrat-e Rasool General Hospital, School of Medicine,Iran University of Medical Sciences, Tehran, Iran Nastaran Khodakarim Department of Medical Oncology and Hematology, Hazrat-e Rasool General Hospital, Iran University of Medical Sciences, Tehran, Iran Marzieh Ghalamkari Department of Medical Oncology and Hematology, Hazrat-e Rasool General Hospital, Iran University of Medical Sciences, Tehran, Iran Fatemeh Tajik Rostami Department of Medical Oncology and Hematology, Hazrat-e Rasool General Hospital, Iran University of Medical Sciences, Tehran, Iran Amineh Salem Department of Medical Oncology and Hematology, Hazrat-e Rasool General Hospital, Iran University of Medical Sciences, Tehran, Iran 2026 06 25 2026 07 13 Background: The production of autoantibodies in cancer patients is a recognized phenomenon, yet their clinical significance and diagnostic yield remain debated. This study evaluated the frequency of rheumatologic autoantibodies in treatment-naïve patients and their association with clinical parameters. Materials and Methods: In this case-control study, 150 treatment-naïve cancer patients (50 lymphoma, 50 breast cancer, 50 GI cancers) and 150 matched healthy controls were enrolled. A broad rheumatologic panel was performed. Clinical staging and molecular subtyping were recorded, and the 24-month progression-free survival (PFS) was also evaluated in a DLBCL subgroup to assess the prognostic weight of ANA and RF positivity. Results: ANA and RF positivity were significantly more prevalent in cancer patients (particularly breast and lymphoma) than in controls. However, specific markers (anti-dsDNA, anti-CCP) were almost entirely negative. In lymphoma, aggressive types showed higher numerical autoantibody positivity than indolent forms, though not reaching statistical significance (p‑value <0.05). ANA and RF positivity were not significantly associated with 2-year PFS in the DLBCL subgroup (p > 0.05). In breast and GI cancers, no consistent correlation was found between ANA status and molecular subtypes or histology. Conclusion: While ANA and RF may be positive in malignancy due to immune dysregulation, these findings are largely non-specific. In the absence of clinical rheumatic symptoms, extensive autoantibody screening does not provide additional diagnostic or prognostic value and should neither prompt a diagnosis of a rheumatic disease nor alter the oncological treatment plan. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/2700 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/2700/1142