Niigata University Hospital is a regional center institution of cancer therapy where many patients with gastrointestinal stromal tumors (GISTs) are visiting to seek the latest treatment. During the time I was treating GIST patients there with imatinib, a tyrosine kinase inhibitor, a small concern was raised: I successively encountered patients who were newly diagnosed as having malignant neoplasms during the course of their treatment. Of the 70 GIST patients who were enrolled in our prospective study of imatinib therapy, seven suffered from second primary malignancies (SPMs). One female GIST patient who suffered from advanced esophageal cancer died of the SPM, whereas the remaining six patients continued with their imatinib therapy and their prognoses were not affected by their SPMs. I reported on the risk of SPMs in GIST patients under imatinib therapy to an international journal of clinical oncology (1). As the patient cohort of our study was so small in number to apply to statistical analysis, our observation was no more than a clinical alert.