Abstract Biopterin as a stable metabolite is produced by oxidation of 5,6,7,8-tetrahydrobiopterin (BH4). It is known that many diseases may cause changes in BH4 concentration and/or dihydropteridine reductase (DHPR) enzyme activity. There is only a limited number of studies correlating DHPR activity in malignancies. The main goal of the present study was to evaluate alterations in the DHPR activity and biopterin levels in patients with breast and thyroid cancers. The breast cancer patients (n=24) were compared to patients with benign breast diseases (n=19) and controls (n=30). In addition; the patients with thyroid cancer (n=17) were compared to patients with benign thyroid diseases (n=42) and the control group. We did not observe any significant difference between the benign disorders and the malignancies. Biopterin concentrations in patients with benign and malign thyroid and breast diseases were lower than the controls (all p <0.05). DHPR activities in thyroid diseases were significantly higher than the controls while insignificant decreases in DHPR activities in breast patients were detected. Our results suggested significant alterations in unconjugated pteridine pathway in thyroid and breast disorders.