Chronic ultraviolet B (UVB) exposure of human or murine skin is known to induce cutaneous photoaging and enhanced carcinogenic risk. An extract of Polypodium leucotomos (PL), a tropical fern plant, has been known to exhibit interesting antioxidant and photoprotective properties against acute exposure to ultraviolet radiation. The objective of this preliminary (or pilot) study was to determine the photoprotective role of topically applied Polypodium leucotomos extract in the prevention or amelioration of cutaneous changes of photoaging in hairless mice. PL-treated mice showed significant reduction of skinfold thickness than those observed in PL-untreated controls. Additionally, PL-treated mice showed a significantly lower degree of histologic parameters of photoaging damage, including dermal elastosis, compared with positive control mice. Interestingly, PL treatment also showed reduction in the number of mice showing skin tumors at 8 weeks after the cessation of the UVB exposure protocol. The results of this preliminary study illustrate that PL treatment helped to ameliorate and to partially inhibit some of the histologic damage associated with photoaging of skin and appeared to contribute to a decrease in the prevalence of UVB-induced skin tumors in mice.