The protein tyrosine kinases (PTKs) diverged specifically in animal lineages by gene duplications and domain shufflings to form a large protein family comprising diverse subfamilies with distinct domain organizations and functions. On the basis of a phylogenetic tree inferred from a comparison of the shared kinase domains, we previously showed that gene duplications that gave rise to diverse subfamilies predate the divergence of parazoans and eumetazoans. There is, however, still a possibility that, although the kinase domain duplications are ancient events, the domain shufflings that gave rise to different subfamilies with distinct domain organization are more recent event than the kinase domain duplications. To clarify this problem, we have determined the complete sequences of 15 sponge PTKs and have compared the domain organizations of these sponge PTKs and those of eumetazoans. For each of ten sponge PTKs out of 15 analyzed here, a possible eumetazoan (human and Drosophila) ortholog has been identified. The sponge and eumetazoan orthologs are virtually identical in domain organization and belong to the same subfamily in the PTK family tree for each of ten orthologous pairs, except for one subfamily in which a considerable deletions and/or insertions of domains are observed. This result suggests that most, if not all, of the domain shufflings, together with gene duplications, are very old, going back to dates before the parazoan-eumetazoan split, the earliest divergence among extant animal phyla.