The signal transduction and transcriptional activation factor 3 (STAT3) plays important roles in many physiological and pathological processes. Although STAT3 is not a classic member of master transcription factors of epithelial-mesenchymal transition (EMT), STAT3 has recently also been documented to be a mediator of tumor cell phenotypic plasticity, in turn affecting formation and phonotypic characteristic of circulating tumor cells, which are associated with invasion and metastases of tumor cells. Activation of STAT3 can translocate into the nucleus and bind to specific promoter sequences of various EMT master transcription factors such as Twist, Snail, and Slug, resulting in the initiation and resolution of EMT programs in malignant cells, which promotes invasion and metastases of developing tumors. On the other hand, inactivated STAT3 may also function as a molecular adaptor to inhibit EMT programs. Therefore, understanding of the interaction between STAT3 and EMT and its effects on circulating tumor cells may provide new approaches for treatment of metastatic carcinomas.