Recent studies re-initiated scientific interest on the dysfunction of tricarboxylic acid cycle (TCAC) genes. These studies presented strong evidence of the relation of TCAC disorders to various types of cancer tumours in humans. An EU-funded project ‘Defects in the tricarboxylic acid (KREBS) cycle genes in tumourigenesis’ (TCAC IN Cancer) focused on deciphering the role of defects in the metabolism pathway of TCAC in cancer development. Ultimately, the goals of the consortium were to characterise human cancer phenotypes and elucidate the molecular mechanisms involved towards efficient cancer prevention. TCAC IN Cancer brought together the top European cancer researchers in the field. The project’s studies were largely based on previous results by its members and other research groups. These results demonstrate a direct association of cancer predisposition with the defect of at least four TCAC genes. Cellular events and proteins affected by these TCAC defects were elucidated by functional studies using systems biology approaches and transcription profiling. These new findings were used to investigate the relation of other cancer types with TCAC defects. The TCAC IN Cancer project found more evidence and key players for TCAC defect associated tumourigenesis. The TCAC IN Cancer consortium has strengthened European cancer research through effective and integrative interaction of top research groups in the field.