Alitretinoin (9-cis-retinoic acid) is an FDA-approved topical therapy for the treatment of Kaposi sarcoma. Alitretinoin is a naturally occurring endogenous retinoid that binds to and activates all known intracellular retinoic acid receptor (RAR) subtypes α, β, and γ and retinoic X receptor (RXR) subtypes α, β, and γ. Photoaging of the skin is the result of accumulated exposure to solar UV radiation. Several topically applied retinoids have been proven clinically effective for treating the appearance of photoaging. Tretinoin and tazarotene, which have been shown to improve photodamaged skin, bind RAR subtypes only. The theoretic benefit of alitretinoin gel 0.1% (Panretin®) in the treatment of photoaged skin stems from the binding and activation of both RARs and RXRs, which promote the repair mechanisms in damaged skin. The objective of this study was to evaluate the safety and efficacy of topical alitretinoin gel 0.1% in the treatment of photodamaged skin. The treatment was well tolerated by participants (N = 20) and subjectively showed improvement of benign skin lesions (eg, seborrheic keratoses) and precancerous lesions (eg, actinic keratoses). Larger, blinded, controlled trials are needed to investigate the role of this novel retinoid in the treatment of photoaging.