Due to significant advantages, the trend in the field of medical technology is moving towards minimally or even non-invasive examination methods. In this respect, optical methods offer inherent benefits, as does diffuse reflectance imaging (DRI). The present study attempts to prove the suitability of DRI-when implemented alongside a suitable setup and data evaluation algorithm-to derive information from anatomically correctly scaled human capillaries (diameter: [Formula: see text], length: [Formula: see text]) by conducting extensive Monte-Carlo simulations and by verifying the findings through laboratory experiments. As a result, the method of shifted position-diffuse reflectance imaging (SP-DRI) is established by which average signal modulations of up to 5% could be generated with an illumination wavelength of [Formula: see text] and a core diameter of the illumination fiber of [Formula: see text]. No reference image is needed for this technique. The present study reveals that the diffuse reflectance data in combination with the SP-DRI normalization are suitable to localize human capillaries within turbid media.