[123I]-2-iodo-l-phenylalanine and [123I]-2-iodo-l-tyrosine were evaluated in rhabdomyosarcoma tumor-bearing athymic mice by means of dynamic planar imaging (DPI) and dissection. A displacement study with l-phenylalanine was performed to prove the specificity of tracer tumor uptake, and kinetic modeling was applied to the DPI results. Moreover, the biodistribution of both tracers was compared with that of 18F-FDG. Both [123I]-2-iodo-l-phenylalanine and [123I]-2-iodo-l-tyrosine showed fast, high and specific tumor accumulation with no significant difference. However, [123I]-2-iodo-l-phenylalanine was cleared faster from the blood to the bladder in comparison with the tyrosine analogue. Moreover, [123I]-2-iodo-l-phenylalanine tumor uptake equilibrated faster with blood. Dissection showed that [123I]-2-iodo-l-tyrosine slightly accumulated in the liver, which was not the case for the phenylalanine analogue. In contrast to 18F-FDG, both tracers showed low uptake in the heart and normal brain tissue, which is advantageous for tumor detection in these organs. [123I]-2-iodo-l-phenylalanine showed more promising characteristics for oncological imaging as compared with [123I]-2-iodo-l-tyrosine. The former tracer not only demonstrated faster blood clearance but also showed that the tracer uptake in the tumor reached its equilibrium with the blood pool activity faster, which led to faster and better tumor contrast. Moreover, both tracers could overcome an important limitation of 18F-FDGȁ4;its high normal brain uptake.