The presence of aggregated α‐synuclein molecules is a common denominator in a variety of neurodegenerative disorders. Here, we show that α‐synuclein (α‐syn) is an outstanding substrate for the protein tyrosine kinase p72^syk(Syk), which phosphorylates three tyrosyl residues in its C‐terminal domain (Y‐125, Y‐133, and Y‐136), as revealed from experiments with mutants where these residues have been individually or multiply replaced by phenylalanine. In contrast, only Y‐125 is phosphorylated by Lyn and c‐Fgr. Eosin‐induced multimerization is observed with wildtype α‐syn, either phosphorylated or not by Lyn, and with all its Tyr to Phe mutants but not with the protein previously phosphorylated by Syk. Syk‐mediated phosphorylation also counteracts α‐syn assembly into filaments as judged from the disappearance of α‐syn precipitated upon centrifugation at 100,000 × g. We also show that Syk and α‐syn colocalize in the brain, and upon cotransfection in Chinese hamster ovary cells, α‐syn becomes Tyr‐phosphorylated by Syk. Moreover, Syk and α‐syn interact with each other as judged from the mammalian two‐hybrid system approach. These data suggest that Syk or tyrosine kinase(s) with similar specificity may play an antineurodegenerative role by phosphorylating α‐syn, thereby preventing its aggregation.