This paper presents a study of the reaction of thin film niobium/selenium multilayers as a function of layer thickness. Diffraction and calorimetry data show a distinct difference in reactions between films with layer thicknesses above and below 60 Angstrom. The thicker films are shown to nucleate Nb5Se4 heterogeneously at the niobium-selenium interfaces. Thinner films form kinetically stable amorphous reaction intermediates before crystallizing Nb5Se4 homogeneously. The nucleation barrier was measured using a Kissinger analysis demonstrating the kinetic stability of the amorphous intermediate. An energy versus reaction progress diagram is presented that contrasts the two reaction mechanisms.