Translocations of the anaplastic lymphoma kinase (ALK) gene result in the production of a number of oncogenic ALK fusion proteins implicated in tumour development. We have previously shown that X-ALK fusion proteins have differential effects on the proliferation, transformation, and invasion properties of NIH3T3 cells in vitro. In the present study, we have investigated the metastatic potential of various X-ALK expressing cell lines using an experimental lung metastasis assay. We have shown that TPM3-ALK expression bestows higher metastatic capacities than other X-ALK fusion proteins and in addition, that TPM3-ALK fusion protein expression specifically induces changes in cell morphology and cytoskeleton organisation. Co-immunoprecipitation studies demonstrate a specific interaction between TPM3-ALK and endogenous tropomyosin. Together the specific actions of TPM3-ALK on the cytoskeleton organisation offer an interesting hypothesis with respect to the higher cell motility and metastatic potential of this fusion protein.