Optical imaging plays an important role in biomedical research being extremely useful for early detection, screening and image-guided therapy. Lanthanide-doped up-converting nanoparticles were ideally suited for bioimaging because they could be excited in near infrared(NIR) and emit in NIR or visible(VIS). Here, we compared lanthanide doped up-converting NaYF4 and organic fluorophores for application in deep-tissue imaging. For that purpose- tissue phantoms mimicking the natural properties of light scattering by living tissues were prepared. The studies allowed to quantitatively compare optical resolution of different fluorescent compounds, revealing that the NIR photoexcitation was favorable over conventional UV photoexcitation. Optical imaging plays an important role in biomedical research being extremely useful for early detection, screening and image-guided therapy. Lanthanide-doped up-converting nanoparticles were ideally suited for bioimaging because they could be excited in near infrared (NIR) and emit in NIR Or visible (VIS). Here, we compared lanthanide doped up-converting NaYF4 and organic fluorophores for application in deep-tissue imaging. For that purpose- tissue phantoms mimicking the natural properties of light scattering by living tissues were prepared. The studies allowed to quantitatively compare optical resolution of different fluorescent compounds, revealing that the NIR photoexcitation was favorable over conventional UV photoexcitation.