Due to their small size and red-shifted excitation and emission bands, lead sulfide (PbS) near-infrared (NIR) quantum dots (QDs) are potentially promising optical contrast agents for in vivo tumor imaging applications. In this phantom-based study, we correlated PbS NIR QD concentrations to feasible imaging depths. A fluorescence imaging system (FIS) was used to acquire images of QDfilled tumor models, which were embedded in liquid tissue phantoms. For the lowest tested concentration of 200 nM, PbS-QD-filled tumor models could be imaged at a tissue phantom depth of 15 mm. Additionally, the FIS was used to compare the imaging potential of PbS QDs to quantum dots that fluoresce in the visible spectral range. Results indicated that tumor models with photons emitted in the NIR region can be imaged with less distortion than those with photons emitted in the visible spectrum. As the phantom thickness over the tumors was increased from 0 to 1.75 mm, the half-intensity widths of normalized fluorescence images produced by red QDs (acquired peak at ∼645 nm) increased by ∼300%; for NIR QDs (acquired peak at ~880 nm), the widths increased by ∼140%. Due to the decreased scattering effect of the tissue phantoms in the NIR spectral range, the margins of PbS QD images were better defined than those of the corresponding red images.