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Summary: Background: There is still much ambiguity in studies of Sonic hedgehog (Shh) pathways and its dysregulation. Some studies concerning the role of the Shh pathway in basal cell carcinoma (BCC) have been conducted, but there is a lack of studies about Shh pathway dysregulation under the influence of ultraviolet (UV)B radiation. Aim: To evaluate skin expression of Shh, Ptch1, Ptch2, Smo and Gli1 proteins in BCCs with and without the influence of UVB radiation. Methods: In total, 34 healthy controls (HCs) and 42 patients with nodular BCC were recruited into the study. Patients were divided into five groups (A–E), depending on UVB dose received and BCC status. In all skin specimens, expression of Shh, Ptch1, Ptch2, Smo and Gli1 protein was evaluated. Results: Comparing the BCC group with the HC group, there was significantly higher expression of Shh, Ptch1, Ptch2, Smo and Gli1 proteins. Expression of Ptch2, Smo and Gli1 was increased in response to UVB doses of 3 MED (minimal erythema dose), whereas expression of Ptch1 and Shh was unaffected. Conclusion: The lack of change in expression of Shh and Ptch1 after exposure to UVB suggests that the Shh pathway may be activated through a noncanonical pathway under the influence of strong UVB doses. [ABSTRACT FROM AUTHOR]