Differential scanning calorimetry (DSC) is a well-known experimental technique for measuring transformation temperatures such as liquidus and solidus in steels. Precise determination of these temperatures is crucial for accurately setting the solidification model of a large-size casting ingot. Therefore, the objective of this article is to discuss the results obtained with DSC to study the accuracy of determining solidus and liquidus temperatures. In the present study the influences of sample mass, cooling rates and chemical composition were the subject of examination to assess their effects on the variation and reliability of the measured solidus and liquidus for an as-cast steel alloy. The DSC experiments were conducted on two ingot-extracted steel compositions that showed variations, due to macrosegregation. Optical microscopy, scanning electron microscopy equipped with energy dispersive spectroscopy and microhardness measurements were employed to investigate microstructure evolution. Thermodynamic calculations performed using FactSage® software showed a significant difference in comparison with the experimental obtained liquidus and solidus temperatures. A 20 mg mass difference increased the solidification interval by 6 °C. Change in the cooling rate resulted in more influence on the deviation of the liquidus temperature than the solidus. Observations revealed an increase in undercooling with the rise in cooling rate, which resulted in shifting the solidification temperature range to lower temperatures. DSC results showed a mass loss after multiple thermal cycles, resulting in notable differences in the liquidus and solidus temperatures, peak shapes, and amplitudes. The results are discussed in terms of their impact in the optimization of large steel ingot casting.