We present an investigation of the prototypical polymorphic structural transformation from marcasite to pyrite FeS₂ studied by combining annealing experiments and theoretical calculations. These experiments have become possible due to the availability of laboratory-synthesized high-purity marcasite samples. We constructed an annealing temperature, time, and phase composition map of marcasite based on a series of isothermal annealing experiments at different temperatures and heating times. To understand the microscopic mechanisms and pathways of the transformation, we performed theoretical calculations that yield an agreement with the experimental results. Based on the combined results, we show that the transformation of marcasite to pyrite, while thermodynamically favorable, is hindered by a kinetic barrier of the order of 3 eV. As a result, marcasite can remain stable for extended times at temperatures below 450 °C.