The ability to monitor changes in the concentration of hemoglobin in the blood of the skin in real time is a key component to personalized patient care. Since hemoglobin has a unique absorption spectrum in the visible light range, diffuse reflectance spectroscopy is the most common approach. Although the collection of the diffuse reflectance spectrum with an integrating sphere (IS) has several calibration challenges, this collection method is sufficiently user-friendly that it may be worth overcoming the initial difficulty. Once the spectrum is obtained, it is commonly interpreted with a log-inverse-reflectance (LIR) or “absorbance” analysis that can only accurately monitor changes in the hemoglobin concentration when there are no changes to the nonhemoglobin chromophore concentrations which is not always the case. We address the difficulties associated with collection of the diffuse reflectance spectrum with an IS and propose a model capable of retrieving relative changes in hemoglobin concentration from the visible light spectrum. The model is capable of accounting for concentration changes in the nonhemoglobin chromophores and is first characterized with theoretical spectra and liquid phantoms. The model is then used in comparison with a common LIR analysis on temporal measurements from blanched and reddened human skin.