Background/alms: Although reflectance spectrophotometry is often applied to measurement of skin color, raw data of reflectance spectra of normal and lesional skin are difficult to analyze. The purpose of this pilot study was to determine whether measurement of spectral difference in absorbance (SDA) between various skin lesions and normal skin adjacent to them could yield useful information for clinics in dermatology. Methods: We studied spectral reflectance of a total of 173 various skin lesions. After converting obtained reflectance into apparent absorbance A (=log(10)(1/reflectance)), we examined the profile of SDA, that is, A(lesion) -A(normal skin) in the range of 400-700 nm, and compared them with the absorbance spectra of melanin and hemoglobin. Results: SDA of epidermal pigmentary disorders was similar to the absorption spectrum of melanin in vitro, but the cases with intradermal melanin deposition showed a different pattern, reflecting the scattering effect of the dermis. SDA of erythematous lesions was similar to the spectra of either oxygenated or reduced hemoglobin, and varied according to the oxygenated level of cutaneous blood. SDA of lesions with a combination of factors appeared as a simple summation of spectra corresponding to each of the factors. Conclusion: Our method may offer easy and quick detection of major pathophysiological changes in skin lesions.