Metastasis is the major cause of mortality in patients with malignancies; however, the mechanisms of tumor cell dissemination and metastasis formation are obscure. Circulating tumor cells (CTCs) are believed to be a critical step for distant metastasis and are associated with a poor patient prognosis. The precise processes of metastasis formation from CTCs are vague. In the present study, we hypothesize that two CTC cluster-based mechanisms of tumor cell inoculation in ectopic organs may be viable: i) Formation of a micro-cancer embolus due to interception of CTC clusters by small vessels; and ii) formation of micrometastasis in an extravasation-dependent or -independent manner. Pathological evidence of micro-cancer emboli is critical for the verifications of this hypothesis. If proved true, this hypothesis will provide a novel perspective for cancer metastasis and has valuable clinical implications.