Background <p>Hashimoto’s thyroiditis is a common autoimmune thyroid disorder and a leading cause of subclinical hypothyroidism. Tumor markers such as CA 19 − 9 and CA 72 − 4 may also be elevated in certain benign inflammatory conditions. This study aimed to investigate the levels of CA 19 − 9 and CA 72 − 4 in patients with subclinical hypothyroidism due to Hashimoto’s thyroiditis and to evaluate the effects of levothyroxine treatment.</p> Methods <p>This prospective case-control study included 30 patients with subclinical hypothyroidism due to Hashimoto’s thyroiditis and 30 healthy controls matched by age and sex. Serum levels of CA 19 − 9, CA 72 − 4, TSH, free T4, TPOAb, and TgAb were measured at baseline and after 6 weeks of levothyroxine therapy. Additionally, correlations between tumor markers and thyroid function parameters were analyzed.</p> Results <p>Initially, there were no significant differences in CA 19 − 9 and CA 72 − 4 levels between the patient and control groups. Following treatment, a significant decrease in CA 19 − 9 levels was observed in patients who achieved euthyroidism (<i>p</i> = 0.020), whereas no significant change was detected in CA 72 − 4 levels.</p> Conclusions <p>CA 19 − 9 and CA 72 − 4 levels do not appear to differ significantly between patients with subclinical hypothyroidism due to Hashimoto’s thyroiditis and healthy individuals. However, CA 19 − 9 levels may decrease upon restoration of euthyroidism, potentially reflecting a reduction in thyroid-related inflammation. Further studies with larger cohorts and longer follow-up periods are warranted to confirm and clarify these observations.</p>