Circulating tumor cells (CTCs) in blood flow have been believed as an essential biomarker of cancer. The technologies of in vitro and in vivo CTC enrichment and detection suggest although CTCs might play a role of "seed" in metastasis, only the minority of CTCs, probably in the form of CTC clusters, hold the potential to develop a tumor in organs. The detected amount of CTCs might be solely an indicator of tumor burden. To provide new insights into this argument, we take advantage of a safe drug to tune the pacemaker activity of a mouse tumor model to increase the heart rate for a period of time every day during the tumor development. We detect the CTCs in vivo by fast line scanning of a confocal microscope when the heart rate returns to the baseline and find the average CTC amount is significantly elevated in the drugtreated group but the metastases are even less than that of control. Our results imply the detected CTC counts in blood might not be directly related to metastasis. K E Y W O R D S circulating tumor cells, heart rate, in vivo detection, metastasis 1 | INTRODUCTION Cancer metastasis is the main reason for death induced by cancer and makes cancer therapy extremely difficult and complicated. The migration mechanism of tumor cells remains unclear, which is believed involved with the detachment of tumor cells from the primary tumor, their entry to the circulating systems to form the so-called circulating tumor cells (CTCs), the long-term survival of CTCs in circulating sys-