By a combined AFM/X-ray study, we unveil a reconstruction at the organic interface accompanying the Stranski-Kranstanov growth of di-indenoperylene (DIP) deposited on fluorinated cobalt-phthalocyanines (F 16 CoPc). This reconstruction involves an abrupt change in the F 16 CoPc packing in those areas covered by DIP. After the total completion of the first DIP monolayer, the entire F 16 CoPc interfacial layer is reconstructed and eventually becomes buried under the growing DIP film. We demonstrate that the morphological transition from smooth to highly textured heterostructures occurring at a threshold temperature of 70 °C is intimately related to the thermal activation of the reconstruction of the underlying F 16 CoPc layers. This study provides further understanding of the molecular-scale processes that ultimately determine the controlled growth of organic heterojunctions.