The measurement sensitivities of absorbing and fluorescing objects in tissue are compared to determine conditions for which fluorescence data are favorable over those derived from absorption. A simulated human breast volume was used to model the relative perturbation in boundary data caused by a deeply embedded anomaly containing elevated concentrations of theoretical exogenous contrast agents with absorption properties resembling lutetium texaphyrin (LuTex) and Indocyanine Green (ICG). Synthetic data were used to produce quantum yield values representing the transition between conditions favorable to fluorescence versus absorption imaging. The parameters explored include tumor-to-background contrast, background drug concentration, and excitation light filtering efficiency. Drug concentration in the background was the primary factor that determined which contrast mechanism provided the more sensitive measurements. Specifically, fluorescence measurements are favorable if background drug concentrations are below 135-200 nM for LuTex and 25-50 nM for ICG, while absorption measurements are more sensitive above these ranges.