Prolonged high-energy ball milling of tetracalcium phosphate (TTCP) resulted in a mechanical activation with the formation of nanocrystalline or amorphous domains within the compound. This mechanically activated material demonstrated a completely different thermal behavior compared with highly crystalline TTCP. Differential scanning calorimetry (DSC) measurements indicated the presence of exothermic reactions between 370° and 480° C and between 630° and 930° C for 24 h-milled TTCP, which could be related to conversion to an apatitic phase and calcium oxide (CaO) and crystallization of these products during heating. X-ray diffraction analyses showed that mechanically activated TTCP began converting to an apatitic phase at ∼ 200° C and fully converted to an apatitic phase and amorphous CaO at 600° C, and a crystalline phase of CaO subsequently appeared around 800°-1200° C. Reconversion to TTCP was observed between 1200° and 1400° C. In contrast, crystalline TTCP remained stable up to 500° C and decomposed to an apatitic phase and CaO around 600°-1000° C.