Similar to the “histone code” hypothesis in which epigenetic marks on histone tails expand the information potential of the genetic code, different tubulin isoforms, combined with a panoply of post-translational modifications (PTMs), constitute the so-called “tubulin code”. The tubulin code was proposed to account for subcellular differentiation of distinct microtubule populations that control the activity of several molecular motors. One of these PTMs consists in the catalytic removal of the c-terminal tyrosine of most mammalian α-tubulin isoforms by tubulin carboxypeptidases (TCPs), such as the recently identified Vasohibin-SVBP complexes, followed by re-tyrosination of soluble α-tubulin by tubulin tyrosine ligase (TTL). α-tubulin detyrosination has been recently implicated in mitosis and meiosis, neuronal processes and cognitive brain function, heart and skeletal muscle contraction, and cancer. In this seminar, I will discuss our work aiming to elucidate how the tubulin code regulates different aspects behind faithful chromosome segregation during mitosis and the implications for human cancers. In particular, I will focus on recent evidence that a-tubulin detyrosination works simultaneously as a navigation system and as a “mitotic error code” to ensure mitotic fidelity.