Orogenic granitoids often display mineralogical and geochemical features suggesting that open-system magmatic processes played a key role in their evolution. This is testified by the presence of enclaves of more mafic magmas dispersed into the granitoid mass, the occurrence of strong disequilibrium textures in mineralogical phases, and/or extreme geochemical and isotopic variability. In this contribution, intrusive rocks constituting the Sithonia Plutonic Complex (Northern Greece) are studied on the basis of mineral chemistry, whole-rock major, trace element geochemistry, and Sr and Nd isotopic composition. Sithonia rocks can be divided into a basic group bearing macroscopic (mafic enclaves), microscopic (disequilibrium textures), geochemical, and isotopic evidence of magma interaction, and an acid group in which most geochemical and isotopic features are consistent with a magma mixing process, but macroscopic and microscopic features are lacking. A two-step Mixing plus Fractional Crystallization (MFC) process is considered responsible for the evolution of the basic group. The first step explains the chemical variation in the mafic enclave group: a basic magma, represented by the least evolved enclaves, interacted with an acid magma, represented by the most evolved granitoid rocks, to give the most evolved enclaves. The second step explains the geochemical variations of the remaining rocks of the basic group: most evolved enclaves interacted with the same acid magma to give the spectrum of rock compositions with intermediate geochemical signatures. A convection–diffusion process is envisaged to explain the geochemical and isotopic variability and the lack of macroscopic and petrographic evidence of magma interaction in the acid group. The mafic magma is presumably the result of melting of a mantle, repeatedly metasomatized and enriched in LILE due to subduction events, whereas the acid magma is considered the product of partial melting of lower crustal rocks of intermediate to basaltic composition. It is shown that Sithonia Plutonic Complex offers the opportunity to investigate in detail the complex interplay between geochemistry and magma dynamics during magma interaction processes between mantle and crustal derived magmas.