BACKGROUND Cis-urocanic acid (cis-UCA), formed from the naturally occurring trans-isomer in the epidermis on ultraviolet (UV) radiation, initiates some of the changes leading to UV-induced immunosuppression, but its role in cutaneous carcinogenesis has not been fully investigated. OBJECTIVE To measure the concentration of UCA isomers in the photoexposed and non-photoexposed skin of patients with multiple non-melanoma skin cancer (NMSC), enrolled in different periods of the year, in comparison with control subjects. METHODS UCA isomers were determined by high-performance liquid chromatography analysis in samples from the outer arm (photoexposed site) and buttock (non-photoexposed site) obtained from 20 patients and 19 controls during the winter period (October to April), and from five patients and 11 controls during the summer period (June to September). RESULTS In the winter months, no difference was found between patients and controls in the concentration of UCA or the percentage of cis-UCA in either site. In the summer months, the percentage of cis-UCA in the buttock of patients and controls was similar but it was significantly higher in the arm of the controls (42%) than in the patients (17%). CONCLUSIONS We conclude that different behaviour regarding sun exposure is the most likely explanation for these results, and that the concentration of UCA and its isomers does not reflect a tendency for individuals to develop NMSC.