Oxidative status assessment is an initial step in tumor related studies. To the best of our knowledge, this is the first study considering oxidative activity of both serum and tissue specimens in human basal cell carcinoma (BCC), which is the most common tumor in the world. Concentration of Malondialdehide (MDA) in human basal cell carcinoma (BCC) and individually matched normal skin tissue were examined with spectrophotometery method. Fresh normal and cancerous skin paired tissue was obtained from 60 patients who underwent curative BCC resection at one center in Tehran (Razi hospital). Serum Concentration of Malondialdehide (MDA) in these patients and 55 normal subjects were also measured. MDA level in cancerous tissue of patients with skin BCC (1.0 ± 0.14 ng/g) was significantly (p = 0.001) higher than normal neighboring skin tissue (0.3 ± 0.07 ng/g). A remarkable (Not significant, P = 0.18) increase was found in the serum MDA level in patients with skin BCC (8.0 ± 2.3 ng/ml) in comparison with the control subjects (7.3 ± 2.9 ng/ml). A significant positive correlation (r = 0.276, p = 0.03) was found between Serum MDA and skin tissue MDA for non-affected skin tissue (normal neighboring skin), whereas no significant correlation (p > 0.05) was found for cancerous tissue. Cut-point of 5.2 ng/ml of serum MDA concentration showed a screening sensitivity of 95%. There is an active oxidative process in BCC lesions. Serum MDA concentration can be used either as a screening test or a predictor for tissue MDA concentration.