The heme oxygenase/biliverdin reductase (HO/BVR) pathway enhances cell stress response by degrading excess heme or producing antioxidant and cytoprotective molecules. Recently, members of the HO/BVR system have been proposed as biomarkers for the early diagnosis of free radical-related diseases. In this study, the presence of both the inducible and constitutive HO isoforms (HO-1 and HO-2, respectively) and BVR was evaluated by immunohistochemistry in human skin cancer samples. Moderate/strong immunoreactivities against HO-1, HO-2 and BVR were detected in 100% of the nodular malignant melanoma samples, whereas in basal cell carcinoma specimens these figures were 62%, 88% and 60%, respectively, with a faint/moderate degree of expression. Faint/moderate HO-1, HO-2 and BVR immunoreactivities were detected in 33%, 66% and 100% of melanocytic nevi samples, respectively. In conclusion, HO-1 and HO-2 and BVR were expressed in the cytosols of skin cancer cells, whereas perilesional normal epidermis showed only faint staining, thus leading to the hypothesis that the HO/BVR system is activated in skin cancers.