We report a case of a primary malignant GIST of the liver metastatic to the lung in a 37 years-old man. The liver tumor showed histological feature of a GIST and expressed vimentin, and diffusely exhibited CD117. One year after the resection of the liver mass, the patient developed multiple small lung metastases which completely disappeared with STI-571 (imatinib mesylate – Gleevec) therapy. C.T. or PET did not show any mass in the abdomen. These findings suggest that the liver mass was a primary rather than a metastatic tumour. They also support the hypothesis that GIST could originate from undifferentiated mesenchymal cells capable to differentiate toward a pacemaker cell phenotype, which are present in sites other than the G.I. tract.