The influence of Re and Ru on phase diagram, as-cast microstructure, and segregation behavior has been investigated using a series of 12 experimental nickel-base superalloys derived from the parent alloy CSMX-4. Up to 2 at. pct Re and 4 at. pct Ru were added at the expense of nickel, while all other alloying elements were kept constant. The Re is found to increase the liquidus temperature and to decrease the γ ′-solvus. The Re additions also strongly increase the amount of eutectic and the tendency for microsegregation. The Ru, on the other hand, displays much weaker effects or even no effect at all. The effects of Re on the eutectic formation and on segregation are shown to be related. Calculations based on ThermoCalc software were carried out and compared with the experimental results. ThermoCalc is found to be able to predict the changes in the phase diagram rather well. However, the calculation of the eutectic fraction with the Scheil–Gulliver model is not satisfying, which is due to the one-dimensionality of the model.