We have previously shown that Docetaxel-induced variable degrees of apoptosis in melanoma. In this report, we studied the β-tubulin repertoire of melanoma cell lines and show that class III β-tubulin expression correlated with Docetaxelresistance. Sensitive cells showed low levels of class III β-tubulin with little microtubular incorporation, whereas class III β-tubulin expression was higher in resistant cells and was incorporated into the cytoskeleton. As proof of concept, abrogation of class III by siRNA reverted Docetaxel-resistant cells to a sensitive phenotype, restoring the microtubular polymerisation response and promoting high levels of apoptosis through Bax activation. These results suggest that phenotypic expression of β-tubulin class III in melanoma may help identify patients with melanoma that can respond to taxanes.