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Background and Objectives: Objective methods to assess quantitatively port wine stain (PWS) blanching in response to laser therapy are needed to improve laser therapeutic outcome. Previous studies have attempted to assess objectively PWS color based on point measurement devices. To date, these approaches have typically been limited by a number of factors such as small test area and need for contact. To address these issues, a cross-polarized diffuse reflectance imaging system and color image analysis method has been developed to evaluate quantitatively erythema and melanin content in PWS skin. Study Design/Materials and Methods: A cross-polarized diffuse reflectance system has been constructed to acquire high resolution digital images while minimizing artifacts such as glare, shadowing, and nonuniform illumination effects that can compromise image fidelity. Furthermore, an image analysis algorithm has also been developed to analyze normal and PWS skin in terms of CIEL*a*b* color space parameters. Using the algorithm, images of color space intensity, L*, and saturation, a*, indices have been calculated to extract quantitative metrics of melanin and erythema, respectively. Results: Compared to the cross-polarized diffuse reflectance image, the a* index image enhanced the contrast in regions of high and low erythema and seems to have quasi correlation with the L* index image. In the presented PWS patient example, the relative a* index difference (Da*) image showed less erythema in PWS skin after laser treatment when compared to pre-treatment values. Conclusions: Our cross-polarized imaging system and color image analysis method is a simple, noncontact technique that can indirectly provide quantitative measurement of erythema and melanin content in PWS skin.