We investigated the change in optical properties and vascular parameters to characterize skin tissue from mild photodamage to actinic keratosis (AK) with comparison to a published photodamage scale. Multi-wavelength spatial frequency domain imaging (SFDI) measurements were performed on the dorsal forearms of 55 adult subjects with various amounts of photodamage. Dermatologists rated the levels of photodamage based upon the photographs in blinded fashion to allow comparison with SFDI data. For characterization of statistical data, we used artificial neural networks. Our results indicate that optical and vascular parameters can be used to quantify photodamage and can discriminate between the stages as low, medium, and high grades, with the best performance of ∼70%, ∼76% and 80% for characterization of low- medium- and high-grade lesions, respectively. Ultimately, clinicians can use this noninvasive approach for risk assessment and frequent monitoring of high-risk populations.