Background <p>Thyroid cancer is now the most commonly diagnosed endocrine malignancy over the past decade, with its incidence having risen sharply. Due to its asymptomatic presentation and poor prognosis when detected at advanced stages, early diagnosis of papillary thyroid cancer (PTC) remains a challenge, even with recent medical advancements. Fortunately, serum-based miRNA testing offers a safe, minimally invasive, and repeatable diagnostic tool. Among promising miRNAs, miRNA-155 has emerged as a potential biomarker for diagnosis and prognosis and, miRNA-429 appears to be more variable and cancer-type specific.</p> Objective <p>This study aimed to assess the expression levels of miRNA-155 and miRNA-429 and to evaluate their correlation with patient prognosis in thyroid cancer.</p> Subjects and methods <p>The study cohort comprised 37 patients with benign thyroid tumors, 37 patients with thyroid cancer, and 74 healthy, age- and sex-matched controls. Plasma samples were collected from all participants, and the expression levels of miRNA-155 and miRNA-429 were quantified using quantitative real-time polymerase chain reaction (qPCR).</p> Results <p>miR-155 expression was significantly upregulated in both benign and malignant thyroid tumors compared to controls (<i>p</i> &lt; 0.001), whereas miR-429 expression was markedly downregulated in both tumor groups relative to controls (<i>p</i> &lt; 0.001). Additionally, miR-155 expression shows weak positive correlation with lymph node involvement in patients with thyroid cancer.</p> Conclusion <p>miR-155 appears to be a promising minimally invasive biomarker for thyroid malignancy, while miR-429 cannot reliably distinguish malignant from non-malignant lesions; further studies are needed to validate these findings.</p>